The Effects of Low Dose Atropine on Choroidal Thickness
Condition: Myopia
MeSH terms: Myopia
Study type: Interventional
Phase: Phase 4

Summary: 
      Atropine eye drops are considered to be an effective form of myopia control in human eyes.
      However, the mechanism by which it exerts it effects are not fully understood. Thickening of
      the choroid subsequent to atropine administration may play an important role in the
      mechanisms by which atropine induces myopia control. Literature also notes that choroidal
      thickness undergoes diurnal variations, which is a variable that will be controlled in this
      study in order to examine atropine's effects on different baseline choroidal thicknesses.

      The purpose of the proposed study is to characterize better the influence of atropine on
      choroid thickness. The study aims are to:

        1. Determine the effect of low dose concentration of topical atropine (0.1% and 0.01%) on
           choroid thickness

        2. Determine the effect of topical atropine on choroid thickness in relationship to
           baseline thickness throughout the day and after one week of daily instillation

      Hypothesis: Atropine's effect on choroidal thickness will be dependent on the subject's
      baseline thickness measurements, at a designated time of the day when the choroid is at its
      thinnest.
    

Detailed description: 
      Atropine eye drops are an effective form of myopia control in children with progressive
      myopia1, but the mechanism in which this occurs is still not fully understood.

      The choroid has been established to play a significant role in the modulation of ocular
      growth in the chick eye;2 eyes with thicker choroids grow slower than eyes with thinner
      choroids.3 Choroidal compensation has also been discovered in other animal species including
      tree shrews,4 marmosets,5 rhesus macaques,6 guinea pigs,7, 8 and even in humans.9, 10 A study
      in humans demonstrated how the thickening of the choroid subsequent to atropine use may
      contribute to the mechanisms by which atropine induces myopia control.11 These results are
      supported by another study where children with less choroidal thickening over time exhibited
      faster axial growth.12 Furthermore, diurnal variation in choroidal thickness has been
      documented13, 14 and individuals with thinner choroids exhibited less variation in thickness
      across the day. 13

      Currently, atropine is prescribed by eye care providers on a daily basis and administered at
      night for convenience. However, choroidal thickness undergoes diurnal variations13, and the
      efficacy of atropine on myopia control in relationship to the patient's baseline choroidal
      thickness is unknown.

      A preliminary study shows that atropine 1% has an effect on reducing choroidal thinning
      throughout the day, but how this translates to low concentration atropine as is commonly
      prescribed in myopia control treatment is unknown. Specifically, preliminary results reveal
      that the maximal pharmaceutical effects on choroidal thickening occurred one hour after
      atropine 1% instillation in the morning, but its relative efficacy during specific time
      points and duration of the day is still unclear. Also, baseline diurnal measurements
      demonstrate that the choroid thins in the morning, is thinnest at noon, and gradually
      thickens in the evening and overnight. The effects of atropine on the choroid from noon to
      the afternoon were not explicitly measured in our previous study, and therefore, are
      measurements of interest. While it is critical to understand the effects of low dose atropine
      on choroidal thickness throughout the evening as commonly prescribed clinically, it is
      important to also understand its effects when the choroid is shown to thin during the day.
      Additionally, the study measured changes in choroidal thickness after one instillation of
      atropine, but did not explore the effects of daily instillation on choroidal thickness and
      whether there is further minimization of choroidal thinning.

      Thus, the objective of this study is to provide data to characterize the influence of low
      dose atropine on choroid thickness. The study aims are:

        1. To determine the effect of low dose topical atropine (0.1% and 0.01%) on choroid
           thickness

        2. To determine the effect of topical atropine on choroid thickness in relationship to
           baseline thickness throughout the day and after one week of daily instillation.

      It is hypothesized that atropine's effect on choroidal thickness will be dependent on the
      subject's baseline thickness measurements, at a designated time of the day when the choroid
      is at its thinnest.

      Potential risks of this study are related to the use of atropine eye drops. Atropine 0.1% and
      0.01% eye drops may cause dilation of the pupil (mydriasis) and paralysis of accommodation
      (cycloplegia).15 There are also rare ocular and systemic adverse effects associated with the
      use of atropine eye drops as described in section C3 below.15 However, using the minimum
      dosage in combination with low concentrations of the drug will minimize these adverse effects
      associated with atropine.16 Participants will be asked if they have experienced any reactions
      to eye drops in the past. The puncta can be occluded as a preventative measure against
      systemic absorption. Risks can be further minimized by preparing for adverse systemic side
      effects and by immediate recognition of the signs and appropriate monitoring. The participant
      will also be educated to report any unforeseen side effects from instillation of the atropine
      according to the instructions detailed in consent form. All participants will be trained to
      promptly report any side effects to the investigators.

      Medline and Pubmed databases were used for literature review.
    

Intervention name(s): Atropine; Atropine
Intervention type(s): Drug; Drug
Intervention description(s): Atropine 0.01% then atropine 0.1%; Atropine 0.1% then atropine 0.01%
Other intervention name(s): Atropine 0.01%; Atropine 0.1%; Atropine 0.1%; Atropine 0.01%
Intervention MeSH terms: Atropine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Atropine