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

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusions:</i></b> 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.

Studies on the interactions of retinal dopamine with choroidal thickness in the chicken

“…All injections were performed under mild ether anesthesia. The intravitreal injection procedure in the chicken is well established (e.g., [11,[24][25][26]) and, as in previous studies, we never observed ocular inflammations.…”

“…We had previously found that intravitreal atropine causes prominent, but transient, choroidal thickening in the chicken eye. The effect was also observed in the contralateral eye where it was more transient [11]. Time courses and magnitudes of choroidal thickness changes in atropine-injected eyes and their saline-injected fellow eyes closely matched observations from our previous study [11].…”

“…Choroidal response can be used for assessment of long-term treatment outcomes …." Also in chickens, atropine caused prominent choroidal thickening although the changes were transient and lasted only a few hours [11]. It is clear that a better understanding of the retinal signals that alter choroidal thickness is needed.…”

Effect of 0.01% Atropine on Accommodation in Myopic Teenagers

“…These findings suggest that the improved effect of 0.01% atropine eye drop instillation on SE might be affected by the shortened AL. Recently, it has been reported that one of the effects of atropine is that it stimulates choroidal thickening ( Chiang et al, 2020 ; Mathis et al, 2021 ; Ye et al, 2021 ). However, our findings were specifically created to have opposing effects at 6 months after atropine eye drop instillation.…”

Transient Eye Shortening During Reading Text With Inverted Contrast: Effects of Refractive Error and Letter Size

“…The hypothesis can probably be best supported by long-term studies in children, 21 , 22 although it may be difficult to finally determine what is cause or consequence. 13 , 23 – 25 …”