Probing the Potency of Artificial Dynamic ON or OFF Stimuli to Inhibit Myopia Development

Wang, Min; Aleman, Andrea Carrillo; Schaeffel, Frank

doi:10.1167/iovs.18-26471

Cited by 28 publications

(30 citation statements)

References 55 publications

(64 reference statements)

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“…We had found earlier [31-34] that OCT represents a fast and convenient technique to measure choroidal thickness in alert chickens. Chicks were held by hand in front of an OCT (HRA + OCT Spectralis, SN 10543, 04/2016, Heidelberg Engineering; resolution mode: high speed, scan angle: 30°, scan type: B-scan, 768 × 496 pixels, line scan, eye tracking not engaged, scan rate: of the live image 8.8 frames/s, and measurements at 1,060 nm).…”

Section: Methodsmentioning

confidence: 99%

“…Misalignment of eyes during image capture resulted in tilting of scans, which was used as an indicator of the same and a need for realignment. Choroidal thickness was manually measured as the distance from the retinal pigment epithelium to the outer boundary of the choroid [34], using the publicly available software ImageJ (https://imagej.nih.gov/ij/). While the quality of the OCT scans of the fundal layers in alert chickens was not comparable to the quality of the scans in human fundal OCT imaging, the measurement procedure had undergone considerable testing and verification in the past in our laboratory.…”

Section: Methodsmentioning

confidence: 99%

“…While the quality of the OCT scans of the fundal layers in alert chickens was not comparable to the quality of the scans in human fundal OCT imaging, the measurement procedure had undergone considerable testing and verification in the past in our laboratory. An interobserver correlation analysis for the OCT measurements of choroidal thickness was performed in a previous study in which both observers were blinded with regard to the treatment of the chickens [34] and showed a correlation coefficient of R = 0.937. In the current study, standard deviations from repeated measurements in the same eyes ranged from 4 to 10 µm, considerably smaller than the interindividual variability among different eyes (between 20 and 50 µm).…”

Section: Methodsmentioning

confidence: 99%

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Effects of Single and Repeated Intravitreal Applications of Atropine on Choroidal Thickness in Alert Chickens

2021

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Introduction: Atropine, a muscarinic antagonist, is known since the 19th century to inhibit myopia development in children. One of its effects is that it stimulates choroidal thickening. Thicker choroids, in turn, have been linked to myopia inhibition. We used the atropine-stimulated choroidal response in the chicken to learn more about the time courses and amplitudes of the effects of atropine, as well as whether repeated applications lead to accumulation or desensitization. Methods: Intravitreal injections containing 250 µg atropine sulfate were performed in 1 eye around 10:00 in the morning, the fellow eye received vehicle. Chickens with bilateral vehicle injections served as controls. Choroidal thickness was measured over the day for every 2–3 h in alert animals, using spectral domain optical coherence tomography, with 3–5 independent measurements in each eye. Three experiments were done – (1) single injection and time course measured over 1 day, (2) single injection and time course measured over 4 days, and (3) daily injections and time course measured over 4 days for measuring the effects of atropine on vitreal, retinal, and choroidal dopamine, and 3,4-dihydroxyphenylacetic acid levels by using high-performance liquid chromatography with electrochemical detection. Results: Atropine induced an increase in choroidal thickness by about 60 percent, with a peak amplitude after about 2 h. The effect persisted only for a few hours and had nearly disappeared by evening. Initially, similar amounts of choroidal thickening were observed in vehicle-injected fellow eyes but recovery to baseline was faster. When atropine was injected daily for 4 days, choroids thickened every day with similar amplitudes and time courses, with no signs of either accumulation or desensitization effects. Interestingly, while dopamine release from the retina was stimulated by atropine and followed approximately, the time course of choroidal thickening, its tissue concentration dropped in the choroid. Conclusions: Even at relatively high intravitreal doses, effects of atropine on choroidal thickness remained transient, similar to its effects on retinal dopamine. With repeated application every day, the diurnal patterns of choroidal thickening could be reproduced for 4 days with similar amplitudes and time courses. The transient nature of the effects of atropine on the choroid may be relevant for application protocols of atropine against myopia.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Effects of Single and Repeated Intravitreal Applications of Atropine on Choroidal Thickness in Alert Chickens

2021

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“…Care was taken to capture OCT images from the center of the fundus. The ChT was measured as the distance from the RPE layer to the outer boundary of the choroid as described recently [37]. There is a visible line between the scleral fibrous layer and cartilaginous layer in B-scan OCT images in chicks [38], and the public software package ImageJ was used to manually determine the thickness of the cartilaginous and fibrous sclera.…”

Section: Measurement Of Refraction (Re) and Axial Length (Al)mentioning

confidence: 99%

Effects of 7-Methylxanthine on Deprivation Myopia and Retinal Dopamine Release in Chickens

Liu

Schaeffel

Trier³

et al. 2019

Ophthalmic Res

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Introduction: Intake of 7-methylxanthine (7-MX), an adenosine receptor (AR) antagonist, has been shown to inhibit school myopia in children and deprivation myopia in rhesus monkeys, but the underlying mechanisms are not known. Also retinal dopamine seems to be involved in the control of eye growth, and in the brain, ARs and dopamine receptors interact widely by heteromerization. We have studied whether 7-MX can inhibit deprivation myopia also in chickens and whether inhibition may involve the retinal dopamine system. Methods: 7-MX was applied by either tubefeeding (100 µg/g body weight, twice a day) or intravitreal injection (12.5 µg, every other day). Forty-eight 2-week-old chicks wore unilateral diffusers and were randomly assigned to either the tube-feeding group (involving 7-MX, vehicle [xanthan gum], or no feeding, for 13 days) or the intravitreal injection group (involving 7-MX, vehicle, or DMSO, for 8 days). Refractions (REs), ocular biometry (AL, VCD), and scleral and choroidal thickness (ChT) were measured before and after treatment. Dopamine and dihydroxyphenylacetic acid (DOPAC) content were determined in retina and vitreous by HPLC at the end of the experiments. Results: No matter how 7-MX was applied, it did not inhibit deprivation myopia in chicks. No significant differences were observed in RE, VCD, AL, and scleral fibrous layer thickness. Feeding 7-MX produced more choroidal thinning in the open contralateral eye compared to control eyes in the vehicle-fed group (-40 ± 14 vs. -1 ± 7 µm, unpaired t test, p < 0.05). DOPAC and dopamine concentration in vitreous and DOPAC concentration in retina did not change with 7-MX. Vitreal dopamine content was significantly decreased in deprived eyes in the groups fed with the vehicle xanthan gum (paired t test, p < 0.01) but not in 7-MX-treated eyes, perhaps indicating a small effect of 7-MX on dopamine. Conclusions: In our study, 7-MX had no effect on DM in chicks and only minor effects on ChT and retinal dopamine. It remains unclear whether 7-MX inhibits myopia through a retinal mechanism or whether it acts directly on choroid and sclera. In the latter case, the finding that myopia is suppressed in mammals but not birds might be explained by differences in scleral structure.

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“… 32 The human choroid responds to short-term overstimulation of the retinal ON- and OFF-pathways, when viewing distant visual targets, by demonstrating a thickening and thinning, respectively. 33 , 34 …”

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confidence: 99%

Retinal OFF-Pathway Overstimulation Leads to Greater Accommodation-Induced Choroidal Thinning

Hoseini-Yazdi

Read

Alonso‐Caneiro

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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Purpose To examine the interactions between accommodation and overstimulation of the retinal ON- and OFF-pathways, and their association with changes in choroidal thickness (ChT) and vascularity. Methods Optical coherence tomography imaging of the choroid of twenty young adults (ages 25 ± 5 years) was performed before and after a series of 30-minute-long viewing tasks, including reading a bright text on dark background (ON-pathway overstimulation) and dark text on bright background (OFF-pathway overstimulation), and a control task of viewing a movie with unbiased ON-/OFF-pathway activation. The viewing tasks were performed with relaxed, and 5 diopter (D) accommodation (induced by soft contact lenses) demands. Both reading texts were matched for the mean luminance (35 cd/m 2 ), luminance contrast (87%), and letter size (approximately 11.8 arc minutes). The change in ChT from baseline associated with contrast polarity and accommodation was examined using linear mixed model analysis. Results The subfoveal ChT decreased significantly by −7 ± 1 µm with 5 D accommodation compared with relaxed accommodation (−3 ± 1 µm; P < 0.001), and by −9 ± 1 µm with OFF-pathway compared with ON-pathway overstimulation (−4 ± 1 µm; P = 0.002) and the control condition (−2 ± 1 µm; P < 0.001). Overstimulation of the OFF-pathway, but not the ON-pathway, resulted in a significantly greater choroidal thinning compared with the control condition, both at relaxed (−7 ± 1 µm; P = 0.003) and 5 D (−11 ± 1 µm; P = 0.005) accommodation levels. Similar changes were also observed for macular total, stromal, and luminal ChT. Conclusions Retinal OFF-pathway stimulation enhanced the choroidal thinning associated with accommodation, thereby providing a potential mechanism that involves accommodation and the retinal OFF-signaling pathway, linking near work and myopia.

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Probing the Potency of Artificial Dynamic ON or OFF Stimuli to Inhibit Myopia Development

Cited by 28 publications

References 55 publications

Effects of Single and Repeated Intravitreal Applications of Atropine on Choroidal Thickness in Alert Chickens

Effects of Single and Repeated Intravitreal Applications of Atropine on Choroidal Thickness in Alert Chickens

Effects of 7-Methylxanthine on Deprivation Myopia and Retinal Dopamine Release in Chickens

Retinal OFF-Pathway Overstimulation Leads to Greater Accommodation-Induced Choroidal Thinning

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