Delayed melatonin circadian timing, lower melatonin output, and sleep disruptions in myopic, or short-sighted, children.

STUDY OBJECTIVES: This study investigated the differences in melatonin circadian timing and output, sleep characteristics, and cognitive function in myopic and non-myopic (or emmetropic) children, aged 8-15 years. METHODS: Twenty-six myopes (refractive error [mean ±â€…standard error mean] -2.06 ±â€…0.23 diopters) and 19 emmetropes (-0.06 ±â€…0.04 diopters), aged 11.74 ±â€…2.31 years were recruited. Circadian timing was assessed using salivary dim-light melatonin onset (DLMO), collected half-hourly for 7 hours, beginning 5 hours before and finishing 2 hours after individual average sleep onset in a sleep laboratory. Nocturnal melatonin output was assessed via aMT6s levels from urine voids collected from 05:30 pm to 8:00 am the following morning. Actigraphy-derived objective sleep timing were acquired for a week prior to the sleep laboratory visit. Cognitive assessments of sustained attention (using psychomotor vigilance task [PVT]) and working memory (using digit spans) were performed on the night of sleep laboratory. RESULTS: Myopic children (9:07 pm ±â€…14 minutes) exhibited a DLMO phase-delay of 1 hour 8 minutes compared to emmetropes (7:59 pm ±â€…13 minutes), p = 0.002. aMT6s melatonin levels were significantly lower among myopes (18.70 ±â€…2.38) than emmetropes (32.35 ±â€…6.93, p = 0.001). Myopes also exhibited significantly delayed sleep onset, delayed wake-up time, poor and reduced sleep, and more evening-type diurnal preference than emmetropes (all p < 0.05). Finally, myopes showed a slower reaction time in the PVT (p < 0.05), but not digit span tasks at night. CONCLUSIONS: These findings suggest a potential association between circadian rhythm dysfunction and myopia in children.

Role of noninvasive ocular imaging as a biomarker in peripheral artery disease: A systematic review.

This study aimed to review the current literature exploring the utility of noninvasive ocular imaging for the diagnosis of peripheral artery disease (PAD). Our search was conducted in early April 2022 and included the databases Medline, Scopus, Embase, Cochrane, and others. Five articles were included in the final review. Of the five studies that used ocular imaging in PAD, two studies used retinal color fundus photography, one used optical coherence tomography (OCT), and two used optical coherence tomography angiography (OCTA) to assess the ocular changes in PAD. PAD was associated with both structural and functional changes in the retina. Structural alterations around the optic disc and temporal retinal vascular arcades were seen in color fundus photography of patients with PAD compared to healthy individuals. The presence of retinal hemorrhages, exudates, and microaneurysms in color fundus photography was associated with an increased future risk of PAD, especially the severe form of the disease. The retinal nerve fiber layer (RNFL) was significantly thinner in the nasal quadrant in patients with PAD compared to age-matched healthy individuals in OCT. Similarly, the choroidal thickness in the subfoveal region was significantly thinner in patients with PAD compared to controls. Patients with PAD also had a significant reduction in the retinal and choroidal circulation in OCTA compared to healthy controls. As PAD causes thinning and ischemic changes in retinal vessels, examination of the retinal vessels using retinal imaging techniques can provide useful information about early microvascular damage in PAD. Ocular imaging could potentially serve as a biomarker for PAD.

Associations between systemic melatonin and human myopia: A systematic review.

PURPOSE: Experimental models have implicated the role of melatonin circadian rhythm disruption in refractive error development. Recent studies have examined melatonin concentration and its diurnal patterns on refractive error with equivocal results. This systematic review aimed to summarise the literature on melatonin circadian rhythms in myopia. RECENT FINDINGS: PubMed, EMBASE, Web of Science, Scopus, ProQuest Central, LILACS, Cochrane and Medline databases were searched for papers between January 2010 and December 2022 using defined search terms. Seven studies measured melatonin and circadian rhythms in three biological fluids (blood serum, saliva and urine) in both myopes and non-myopes. Morning melatonin concentrations derived from blood serum varied significantly between studies in individuals aged 10-30 years, with a maximum of 89.45 pg/mL and a minimum of 5.43 pg/mL using liquid chromatography and mass spectrometry. The diurnal variation of salivary melatonin was not significantly different between myopes and emmetropes when measured every 4 h for 24 h and quantified with enzyme-linked immunosorbent assay. Significantly elevated salivary melatonin concentrations were reported in myopes compared with emmetropes, aged 18-30 years when measured hourly from evening until their habitual bedtime using liquid chromatography. However, the relationship between dim light melatonin onset and refractive group was inconsistent between studies. The 6-sulphatoxymelatonin concentration derived from overnight urine volume, measured using a double antibody radioimmunoassay, was found to be significantly lower in myopes (29.17 pg/mL) than emmetropes (42.51 pg/mL). SUMMARY: The role of melatonin concentration and rhythm in myopia has not been studied extensively. This systematic review confirms conflicting findings across studies, with potential relationships existing. Future studies with uniform methodological approaches are required to ascertain the causal relationship between melatonin dysregulation and myopia in humans.

Association between relative peripheral refraction and corresponding electro-retinal signals.

PURPOSE: Considering the potential role of the peripheral retina in refractive development and given that peripheral refraction varies significantly with increasing eccentricity from the fovea, we investigated the association between relative peripheral refraction (RPR) and corresponding relative peripheral multifocal electroretinogram (mfERG) responses (electro-retinal signals) from the central to the peripheral retina in young adults. METHODS: Central and peripheral refraction using an open-field autorefractor and mfERG responses using an electrophysiology stimulator were recorded from the right eyes of 17 non-myopes and 24 myopes aged 20-27 years. The relative mfERG N1, P1 and N2 components (amplitude density and implicit time) of a mfERG waveform were compared with the corresponding RPR measurements at the best-matched eccentricities along the principal meridians, that is at the fovea (0°), horizontal (±5°, ±10° and ± 25°) and vertical meridians (±10° and ± 15°). RESULTS: The mean absolute mfERG N1, P1 and N2 amplitude densities (nV/deg2 ) were maximum at the fovea in both non-myopes (N1: 57.29 ± 14.70 nV/deg2 , P1: 106.29 ± 24.46 nV/deg2 , N2: 116.41 ± 27.96 nV/deg2 ) and myopes (N1: 56.25 ± 15.79 nV/deg2 , P1: 100.79 ± 30.81 nV/deg2 , N2: 105.75 ± 37.91 nV/deg2 ), which significantly reduced with increasing retinal eccentricity (p < 0.01). No significant association was reported between the RPR and corresponding relative mfERG amplitudes at each retinal eccentricity (overall Pearson's correlation, r = -0.25 to 0.26, p ≥ 0.09). In addition, the presence of relative peripheral myopia or hyperopia at extreme peripheral retinal eccentricities did not differentially influence the corresponding relative peripheral mfERG amplitudes (p ≥ 0.24). CONCLUSIONS: Relative peripheral mfERG signals are not associated with corresponding RPR in young adults. It is plausible that the electro-retinal signals may respond to the presence of absolute hyperopia (and not relative peripheral hyperopia), which requires further investigation.

Comparison of an open view autorefractor with an open view aberrometer in determining peripheral refraction in children

Purpose: The aim of this study was to compare central and peripheral refraction using an open view Shin-Nippon NVision-K 5001 autorefractor and an open view COAS-HD VR aberrometer in young children.MethodsCycloplegic central and peripheral autorefraction was measured in the right eye of 123 children aged 8 to 16 years. Three measurements each were obtained with both Shin-Nippon NVision-K 5001 autorefractor and COAS-HD VR aberrometer along the horizontal visual field up to 30° (nasal and temporal) in 10° steps. The refraction from the autorefractor was compared with aberrometer refraction for pupil analysis diameters of 2.5-mm and 5.0-mm.ResultsThe Shin-Nippon was 0.30 D more hyperopic than COAS-HD VR at 2.5-mm pupil and 0.50 D more hyperopic than COAS-HD VR at 5-mm pupil for central refraction. For both pupil sizes, the 95% limits of agreement were approximately 0.50 D for central refraction, and limits were wider in the nasal visual field compared to the temporal visual field. The mean difference for both J0 and J45 were within 0.15 D and the 95% limits of agreement within 0.90 D across the horizontal visual field.ConclusionDefocus components were similar between the Shin-Nippon autorefractor and the COAS-HD VR aberrometer with a 2.5-mm pupil for most visual field angles. However, there was a significant difference in defocus component between the Shin-Nippon autorefractor and the COAS-HD VR aberrometer with a 5.0-mm pupil, wherein the autorefractor measured more hyperopia. The astigmatic components J0 and J45 were similar between instruments for both central and peripheral refraction. (AU)

The effect of intrinsically photosensitive retinal ganglion cell (ipRGC) stimulation on axial length changes to imposed optical defocus in young adults

Purpose: The intrinsically photosensitive retinal ganglion cells (ipRGCs) regulate pupil size and circadian rhythms. Stimulation of the ipRGCs using short-wavelength blue light causes a sustained pupil constriction known as the post-illumination pupil response (PIPR). Here we examined the effects of ipRGC stimulation on axial length changes to imposed optical defocus in young adults.Materials and methodsNearly emmetropic young participants were given either myopic (+3 D, n = 16) or hyperopic (-3 D, n = 17) defocus in their right eye for 2 h. Before and after defocus, a series of axial length measurements for up to 180 s were performed in the right eye using the IOL Master following exposure to 5 s red (625 nm, 3.74 × 1014 photons/cm2/s) and blue (470 nm, 3.29 × 1014 photons/cm2/s) stimuli. The pupil measurements were collected from the left eye to track the ipRGC activity. The 6 s and 30 s PIPR, early and late area under the curve (AUC), and time to return to baseline were calculated.ResultsThe PIPR with blue light was significantly stronger after 2 h of hyperopic defocus as indicated by a lower 6 and 30 s PIPR and a larger early and late AUC (all p<0.05). Short-wavelength ipRGC stimulation also significantly exaggerated the ocular response to hyperopic defocus, causing a significantly greater increase in axial length than that resulting from the hyperopic defocus alone (p = 0.017). Neither wavelength had any effect on axial length with myopic defocus.ConclusionsThese findings suggest an interaction between myopiagenic hyperopic defocus and ipRGC signaling. (AU)

Comparison of an open view autorefractor with an open view aberrometer in determining peripheral refraction in children.

PURPOSE: The aim of this study was to compare central and peripheral refraction using an open view Shin-Nippon NVision-K 5001 autorefractor and an open view COAS-HD VR aberrometer in young children. METHODS: Cycloplegic central and peripheral autorefraction was measured in the right eye of 123 children aged 8 to 16 years. Three measurements each were obtained with both Shin-Nippon NVision-K 5001 autorefractor and COAS-HD VR aberrometer along the horizontal visual field up to 30° (nasal and temporal) in 10° steps. The refraction from the autorefractor was compared with aberrometer refraction for pupil analysis diameters of 2.5-mm and 5.0-mm. RESULTS: The Shin-Nippon was 0.30 D more hyperopic than COAS-HD VR at 2.5-mm pupil and 0.50 D more hyperopic than COAS-HD VR at 5-mm pupil for central refraction. For both pupil sizes, the 95% limits of agreement were approximately 0.50 D for central refraction, and limits were wider in the nasal visual field compared to the temporal visual field. The mean difference for both J0 and J45 were within 0.15 D and the 95% limits of agreement within 0.90 D across the horizontal visual field. CONCLUSION: Defocus components were similar between the Shin-Nippon autorefractor and the COAS-HD VR aberrometer with a 2.5-mm pupil for most visual field angles. However, there was a significant difference in defocus component between the Shin-Nippon autorefractor and the COAS-HD VR aberrometer with a 5.0-mm pupil, wherein the autorefractor measured more hyperopia. The astigmatic components J0 and J45 were similar between instruments for both central and peripheral refraction.

The effect of intrinsically photosensitive retinal ganglion cell (ipRGC) stimulation on axial length changes to imposed optical defocus in young adults.

PURPOSE: The intrinsically photosensitive retinal ganglion cells (ipRGCs) regulate pupil size and circadian rhythms. Stimulation of the ipRGCs using short-wavelength blue light causes a sustained pupil constriction known as the post-illumination pupil response (PIPR). Here we examined the effects of ipRGC stimulation on axial length changes to imposed optical defocus in young adults. MATERIALS AND METHODS: Nearly emmetropic young participants were given either myopic (+3 D, n = 16) or hyperopic (-3 D, n = 17) defocus in their right eye for 2 h. Before and after defocus, a series of axial length measurements for up to 180 s were performed in the right eye using the IOL Master following exposure to 5 s red (625 nm, 3.74 × 1014 photons/cm2/s) and blue (470 nm, 3.29 × 1014 photons/cm2/s) stimuli. The pupil measurements were collected from the left eye to track the ipRGC activity. The 6 s and 30 s PIPR, early and late area under the curve (AUC), and time to return to baseline were calculated. RESULTS: The PIPR with blue light was significantly stronger after 2 h of hyperopic defocus as indicated by a lower 6 and 30 s PIPR and a larger early and late AUC (all p<0.05). Short-wavelength ipRGC stimulation also significantly exaggerated the ocular response to hyperopic defocus, causing a significantly greater increase in axial length than that resulting from the hyperopic defocus alone (p = 0.017). Neither wavelength had any effect on axial length with myopic defocus. CONCLUSIONS: These findings suggest an interaction between myopiagenic hyperopic defocus and ipRGC signaling.

Effects of mild- and moderate-intensity illumination on short-term axial length and choroidal thickness changes in young adults.

PURPOSE: Previous studies have shown that time spent outdoors is protective against myopia development in children. In this study, we examined the effects of 500 and 1000 lux of illumination to the eye on axial length (AL) and choroidal thickness (CT) changes in young adults. METHODS: Fifteen participants (mean age, 21.60 years [2.16]) with a mean refraction of -0.34 D (0.37) were exposed to 500 and 1000 lux of illumination for 120 min in a dark room on two different days, using a pair of light-emitting glasses. Ocular measurements were repeated on an additional day in darkness (~5 lux). Ocular biometrics and CT were measured and analysed in the right eye before the light exposure (0 min), after 30, 60 and 120 min of exposure and 30 min after light offset to measure recovery using the Lenstar biometer and the Cirrus optical coherence tomographer, respectively. RESULTS: Exposure to 500 and 1000 lux of illumination resulted in a significant reduction in AL at 30, 60 and 120 min compared to darkness (AL change at 120 min: darkness, +0.020 mm [0.004]; 500 lux, -0.006 mm [0.004]; 1000 lux, -0.013 mm [0.004]; p < 0.001). Exposure to 500 and 1000 lux caused a significant overall thickening of the subfoveal choroid compared to darkness (CT change across 120 min: darkness, -0.010 mm [0.007]; 500 lux, +0.006 mm [0.005]; 1000 lux, +0.009 mm [0.003], p = 0.02). Ocular changes were not significantly different between the two illumination levels (p > 0.05) and returned to baseline within 30 min of light offset. CONCLUSIONS: Exposure to mild- or moderate-intensity illumination on the eye can induce a significant short-term reduction in AL and an increase in CT in young adults. Future studies on larger cohorts with varying light intensities are needed to better understand the effects of ocular illumination on AL changes in humans.

The intrinsically photosensitive retinal ganglion cell (ipRGC) mediated pupil response in young adult humans with refractive errors

Purpose: The intrinsically photosensitive retinal ganglion cells (ipRGCs) signal environmental light, with axons projected to the midbrain that control pupil size and circadian rhythms. Post-illumination pupil response (PIPR), a sustained pupil constriction after short-wavelength light stimulation, is an indirect measure of ipRGC activity. Here, we measured the PIPR in young adults with various refractive errors using a custom-made optical system.Methods: PIPR was measured on myopic (−3.50 ± 1.82 D, n = 20) and non-myopic (+0.28 ± 0.23 D, n = 19) participants (mean age, 23.36 ± 3.06 years). The right eye was dilated and presented with long-wavelength (red, 625 nm, 3.68 × 1014 photons/cm2/s) and short-wavelength (blue, 470 nm, 3.24 × 1014 photons/cm2/s) 1 s and 5 s pulses of light, and the consensual response was measured in the left eye for 60 s following light offset. The 6 s and 30 s PIPR and early and late area under the curve (AUC) for 1 and 5 s stimuli were calculated.Results: For most subjects, the 6 s and 30 s PIPR were significantly lower (p < 0.001), and the early and late AUC were significantly larger for 1 s blue light compared to red light (p < 0.001), suggesting a strong ipRGC response. The 5 s blue stimulation induced a slightly stronger melanopsin response, compared to 1 s stimulation with the same wavelength. However, none of the PIPR metrics were different between myopes and non-myopes for either stimulus duration (p > 0.05).Conclusions: We confirm previous research that there is no effect of refractive error on the PIPR. (AU)

Assessment of patient-reported outcome measures used in corneal transplantation: a systematic review.

The aim of this study was to review all the articles that have implemented patient-reported outcome measures (PROMs) to evaluate the quality of life (QoL) in corneal transplantation and discuss quality assessments of the PROMs. An extensive literature review was undertaken to identify all the studies that used PROMs to assess the QoL in corneal transplantation. Non-original or review articles, articles on other subject area and articles on cost-effectiveness/utility without PROM data/results were excluded. Each PROM was assessed against the following criteria: content development (item identification and item selection), psychometric properties, validity, reliability, and responsiveness. 425 articles were identified of which 35 articles were included in the final review. PROMs in corneal transplantation were used to (a) evaluate the QoL after surgery, (b) compare the QoL scores between different surgical techniques and (c) determine the relationship between QoL and objective measures such as visual acuity, visual field and stereoacuity. A total of 17 PROMs were used to assess QoL in corneal transplantation. Whilst this search did not produce any PROMs that were specifically designed to assess corneal transplantation, most studies were found to have employed the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ 25). The Visual Function Index 14 (VF 14) performed better in the present quality assessment criteria compared to other PROMs, however, the NEI VFQ 25 and the VF 14 PROMs were not specifically developed for corneal transplantation and therefore the QoL assessment made using these PROMs may be incomplete. As improvements in various forms of lamellar transplantation surgery techniques such as UT-DSAEK and FT-DSAEK have resulted in better visual outcomes, improved graft survival and reduced complications, a corneal transplantation specific PROM will be useful in clinical settings to compare the outcomes of different surgical techniques from the patient perspective.

A retrospective evaluation of the Brain and Body Fitness Studio service on functional capacity and quality of life in people with neurological disorders.

Background: People with neurological disorders (ND) are less physically active than the general population due to physical, sensory, and/or cognitive impairments. These individuals often feel intimidated to join mainstream health and wellness centers due to lack of specialized support for people with ND. The Brain and Body Fitness Studio (BBFS) is one of the first Accredited Exercise Physiologist-led interprofessional services in Adelaide South Australia to provide individualized evidence-based multimodal exercise prescription and social support for this population. This comprehensive retrospective study evaluated the impact of BBFS on functional capacity (FC) determined as the 6-min walk distance (6 MWD) achieved during a 6-min walk test (6 MWT), of its members with ND. Methods: Sixty-two BBFS members (age, 66 ± 10 years; 60% male) with ND (85% Parkinson's Disease; average time since diagnosis, 4 years [IQR, 2 to 12 years]) and complete pre- and post-6-month clinical assessment of the primary outcome of the study, the 6 MWD, were included in this retrospective analysis. A series of sub-analyses were also performed to investigate the effects of adherence to the recommended prescription of at least twice a week in the program (≥80 vs. < 80% adherence), and disease stage (time since diagnosis; ≥6 vs. < 6 years) on FC. Results: Although there was no statistically significant change in 6 MWD from pre- to post-6-month BBFS program (+15 ± 90 m, p = 0.19), a clinically meaningful improvement of >14 m was evident. Improvement in 6 MWD was significantly greater in members who attended at least 80% of the recommended visits (≥80% visits, +37 ± 58 m; ≤ 80% visits,-1 ± 105 m, p = 0.046). We also found a 6 MWD improvement from pre- to post-6 months in those in the early years of their ND (< 6 years since diagnosis, +39 ± 76 m), but not in those in the later years of their ND (≥6 years since diagnosis, -36 ± 123 m, between group difference, p = 0.029). Conclusion: A clinically meaningful 6 MWD improvement may be elicited by services provided by BBFS in people with ND. Overall, the benefits appear to be more evident in members who attended the BBFS for at least 80% of the recommended visits and those who were in the early stage of their ND diagnosis.

Electroretinogram responses in myopia: a review.

The stretching of a myopic eye is associated with several structural and functional changes in the retina and posterior segment of the eye. Recent research highlights the role of retinal signaling in ocular growth. Evidence from studies conducted on animal models and humans suggests that visual mechanisms regulating refractive development are primarily localized at the retina and that the visual signals from the retinal periphery are also critical for visually guided eye growth. Therefore, it is important to study the structural and functional changes in the retina in relation to refractive errors. This review will specifically focus on electroretinogram (ERG) changes in myopia and their implications in understanding the nature of retinal functioning in myopic eyes. Based on the available literature, we will discuss the fundamentals of retinal neurophysiology in the regulation of vision-dependent ocular growth, findings from various studies that investigated global and localized retinal functions in myopia using various types of ERGs.

Melanopsin modulates refractive development and myopia.

Myopia, or nearsightedness, is the most common form of refractive abnormality and is characterized by excessive ocular elongation in relation to ocular power. Retinal neurotransmitter signaling, including dopamine, is implicated in myopic ocular growth, but the visual pathways that initiate and sustain myopia remain unclear. Melanopsin-expressing retinal ganglion cells (mRGCs), which detect light, are important for visual function, and have connections with retinal dopamine cells. Here, we investigated how mRGCs influence normal and myopic refractive development using two mutant mouse models: Opn4-/- mice that lack functional melanopsin photopigments and intrinsic mRGC responses but still receive other photoreceptor-mediated input to these cells; and Opn4DTA/DTA mice that lack intrinsic and photoreceptor-mediated mRGC responses due to mRGC cell death. In mice with intact vision or form-deprivation, we measured refractive error, ocular properties including axial length and corneal curvature, and the levels of retinal dopamine and its primary metabolite, L-3,4-dihydroxyphenylalanine (DOPAC). Myopia was measured as a myopic shift, or the difference in refractive error between the form-deprived and contralateral eyes. We found that Opn4-/- mice had altered normal refractive development compared to Opn4+/+ wildtype mice, starting ∼4D more myopic but developing ∼2D greater hyperopia by 16 weeks of age. Consistent with hyperopia at older ages, 16 week-old Opn4-/- mice also had shorter eyes compared to Opn4+/+ mice (3.34 vs 3.42 mm). Opn4DTA/DTA mice, however, were more hyperopic than both Opn4+/+ and Opn4-/- mice across development ending with even shorter axial lengths. Despite these differences, both Opn4-/- and Opn4DTA/DTA mice had ∼2D greater myopic shifts in response to form-deprivation compared to Opn4+/+ mice. Furthermore, when vision was intact, dopamine and DOPAC levels were similar between Opn4-/- and Opn4+/+ mice, but higher in Opn4DTA/DTA mice, which differed with age. However, form-deprivation reduced retinal dopamine and DOAPC by ∼20% in Opn4-/- compared to Opn4+/+ mice but did not affect retinal dopamine and DOPAC in Opn4DTA/DTA mice. Lastly, systemically treating Opn4-/- mice with the dopamine precursor L-DOPA reduced their form-deprivation myopia by half compared to non-treated mice. Collectively our findings show that disruption of retinal melanopsin signaling alters the rate and magnitude of normal refractive development, yields greater susceptibility to form-deprivation myopia, and changes dopamine signaling. Our results suggest that mRGCs participate in the eye's response to myopigenic stimuli, acting partly through dopaminergic mechanisms, and provide a potential therapeutic target underling myopia progression. We conclude that proper mRGC function is necessary for correct refractive development and protection from myopia progression.

The intrinsically photosensitive retinal ganglion cell (ipRGC) mediated pupil response in young adult humans with refractive errors.

PURPOSE: The intrinsically photosensitive retinal ganglion cells (ipRGCs) signal environmental light, with axons projected to the midbrain that control pupil size and circadian rhythms. Post-illumination pupil response (PIPR), a sustained pupil constriction after short-wavelength light stimulation, is an indirect measure of ipRGC activity. Here, we measured the PIPR in young adults with various refractive errors using a custom-made optical system. METHODS: PIPR was measured on myopic (-3.50 ± 1.82 D, n = 20) and non-myopic (+0.28 ± 0.23 D, n = 19) participants (mean age, 23.36 ± 3.06 years). The right eye was dilated and presented with long-wavelength (red, 625 nm, 3.68 × 1014 photons/cm2/s) and short-wavelength (blue, 470 nm, 3.24 × 1014 photons/cm2/s) 1 s and 5 s pulses of light, and the consensual response was measured in the left eye for 60 s following light offset. The 6 s and 30 s PIPR and early and late area under the curve (AUC) for 1 and 5 s stimuli were calculated. RESULTS: For most subjects, the 6 s and 30 s PIPR were significantly lower (p < 0.001), and the early and late AUC were significantly larger for 1 s blue light compared to red light (p < 0.001), suggesting a strong ipRGC response. The 5 s blue stimulation induced a slightly stronger melanopsin response, compared to 1 s stimulation with the same wavelength. However, none of the PIPR metrics were different between myopes and non-myopes for either stimulus duration (p > 0.05). CONCLUSIONS: We confirm previous research that there is no effect of refractive error on the PIPR.

Ambient Light Regulates Retinal Dopamine Signaling and Myopia Susceptibility.

Purpose: Exposure to high-intensity or outdoor lighting has been shown to decrease the severity of myopia in both human epidemiological studies and animal models. Currently, it is not fully understood how light interacts with visual signaling to impact myopia. Previous work performed in the mouse retina has demonstrated that functional rod photoreceptors are needed to develop experimentally-induced myopia, alluding to an essential role for rod signaling in refractive development. Methods: To determine whether dim rod-dominated illuminance levels influence myopia susceptibility, we housed male C57BL/6J mice under 12:12 light/dark cycles with scotopic (1.6 × 10-3 candela/m2), mesopic (1.6 × 101 cd/m2), or photopic (4.7 × 103 cd/m2) lighting from post-natal day 23 (P23) to P38. Half the mice received monocular exposure to -10 diopter (D) lens defocus from P28-38. Molecular assays to measure expression and content of DA-related genes and protein were conducted to determine how illuminance and lens defocus alter dopamine (DA) synthesis, storage, uptake, and degradation and affect myopia susceptibility in mice. Results: We found that mice exposed to either scotopic or photopic lighting developed significantly less severe myopic refractive shifts (lens treated eye minus contralateral eye; -1.62 ± 0.37D and -1.74 ± 0.44D, respectively) than mice exposed to mesopic lighting (-3.61 ± 0.50D; P < 0.005). The 3,4-dihydroxyphenylacetic acid /DA ratio, indicating DA activity, was highest under photopic light regardless of lens defocus treatment (controls: 0.09 ± 0.011 pg/mg, lens defocus: 0.08 ± 0.008 pg/mg). Conclusions: Lens defocus interacted with ambient conditions to differentially alter myopia susceptibility and DA-related genes and proteins. Collectively, these results show that scotopic and photopic lighting protect against lens-induced myopia, potentially indicating that a broad range of light levels are important in refractive development.

Myopia, or near-sightedness, is associated with delayed melatonin circadian timing and lower melatonin output in young adult humans.

STUDY OBJECTIVES: Myopia, or near-sightedness, is the most common refractive vision disorder and predisposes the eye to many blinding conditions in adulthood. Recent research has suggested that myopia is associated with increased endogenous melatonin production. Here we investigated the differences in melatonin circadian timing and output in young adult myopes and non-myopes (or emmetropes) as a pathogenesis for myopia. METHODS: A total of 18 myopic (refractive error [mean ± standard deviation] -4.89 ± 2.16 dioptres) and 14 emmetropic participants (-0.09 ± 0.13 dioptres), aged 22.06 ± 2.35 years were recruited. Circadian timing was assessed using salivary dim light melatonin onset (DLMO), collected half-hourly for 7 h, beginning 5 h before and finishing 2 h after individual average sleep onset in a sleep laboratory. Total melatonin production was assessed via aMT6s levels from urine voids collected from 06:00 pm and until wake-up time the following morning. Objective measures of sleep timing were acquired a week prior to the sleep laboratory visit using an actigraphy device. RESULTS: Myopes (22:19 ± 1.8 h) exhibited a DLMO phase-delay of 1 hr 12 min compared with emmetropes (21:07 ± 1.4 h), p = 0.026, d = 0.73. Urinary aMT6s melatonin levels were significantly lower among myopes (29.17 ± 18.67) than emmetropes (42.51 ± 23.97, p = 0.04, d = 0.63). Myopes also had a significant delay in sleep onset, greater sleep onset latency, shorter sleep duration, and more evening-type diurnal preference than emmetropes (all p < 0.05). CONCLUSIONS: These findings suggest a potential association between circadian rhythms and myopia in humans.

Optical mechanisms regulating emmetropisation and refractive errors: evidence from animal models.

Our current understanding of emmetropisation and myopia development has evolved from decades of work in various animal models, including chicks, non-human primates, tree shrews, guinea pigs, and mice. Extensive research on optical, biochemical, and environmental mechanisms contributing to refractive error development in animal models has provided insights into eye growth in humans. Importantly, animal models have taught us that eye growth is locally controlled within the eye, and can be influenced by the visual environment. This review will focus on information gained from animal studies regarding the role of optical mechanisms in guiding eye growth, and how these investigations have inspired studies in humans. We will first discuss how researchers came to understand that emmetropisation is guided by visual feedback, and how this can be manipulated by form-deprivation and lens-induced defocus to induce refractive errors in animal models. We will then discuss various aspects of accommodation that have been implicated in refractive error development, including accommodative microfluctuations and accommodative lag. Next, the impact of higher order aberrations and peripheral defocus will be discussed. Lastly, recent evidence suggesting that the spectral and temporal properties of light influence eye growth, and how this might be leveraged to treat myopia in children, will be presented. Taken together, these findings from animal models have significantly advanced our knowledge about the optical mechanisms contributing to eye growth in humans, and will continue to contribute to the development of novel and effective treatment options for slowing myopia progression in children.

Altered ocular parameters from circadian clock gene disruptions.

The pathophysiology of refractive errors is poorly understood. Myopia (nearsightedness) in particular both blurs vision and predisposes the eye to many blinding diseases during adulthood. Based on past findings of diurnal variations in the dimensions of the eyes of humans and other vertebrates, altered diurnal rhythms of these ocular dimensions with experimentally induced myopia, and evolving evidence that ambient light exposures influence refractive development, we assessed whether disturbances in circadian signals might alter the refractive development of the eye. In mice, retinal-specific knockout of the clock gene Bmal1 induces myopia and elongates the vitreous chamber, the optical compartment separating the lens and the retina. These alterations simulate common ocular findings in clinical myopia. In Drosophila melanogaster, knockouts of the clock genes cycle or period lengthen the pseudocone, the optical component of the ommatidium that separates the facet lens from the photoreceptors. Disrupting circadian signaling thus alters optical development of the eye in widely separated species. We propose that mechanisms of myopia include circadian dysregulation, a frequent occurrence in modern societies where myopia also is both highly prevalent and increasing at alarming rates. Addressing circadian dysregulation may improve understanding of the pathogenesis of refractive errors and introduce novel therapeutic approaches to ameliorate myopia development in children.