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The Effects of Low Dose Atropine on Choroidal Thickness

Sponsor
State University of New York College of Optometry (Other)
Overall Status
Completed
CT.gov ID
NCT03544827
Collaborator
(none)
36
Enrollment
1
Location
2
Arms
8.6
Actual Duration (Months)
4.2
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
36 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Masking Description:
Participants and main investigator will be blinded to the allocation concealment
Primary Purpose:
Prevention
Official Title:
The Effects of Low Dose Atropine on Choroidal Thickness
Actual Study Start Date :
May 21, 2018
Actual Primary Completion Date :
Feb 8, 2019
Actual Study Completion Date :
Feb 8, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Atropine 0.01% then atropine 0.1%

Participants will be on topical atropine 0.01% ophthalmic solution QD OU for 1 week (7 days) and then topical atropine 0.1% ophthalmic solution QD OU for 1 week (7 days) with a washout period of 4 weeks in between each intervention

Drug: Atropine
Atropine 0.01% then atropine 0.1%
Other Names:
  • Atropine 0.01%
  • Atropine 0.1%

    • Drug: Atropine
    Atropine 0.1% then atropine 0.01%
    Other Names:
  • Atropine 0.1%
  • Atropine 0.01%

    		•
    Experimental: Atropine 0.1% then atropine 0.01%

    Participants will be on topical atropine 0.1% ophthalmic solution QD OU for 1 week (7 days) and then topical atropine 0.01% ophthalmic solution QD OU for 1 week (7 days) with a washout period of 4 weeks in between each intervention

    Drug: Atropine
    Atropine 0.01% then atropine 0.1%
    Other Names:
  • Atropine 0.01%
  • Atropine 0.1%

    • Drug: Atropine
    Atropine 0.1% then atropine 0.01%
    Other Names:
  • Atropine 0.1%
  • Atropine 0.01%

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Choroidal thickness [1 hour, 4 hours, 8 hours, and 1 week from baseline measurement]

      Measure choroidal thickness changes at baseline and compare to choroidal thickness after intervention of atropine 0.01% and atropine 0.1%

    Secondary Outcome Measures

    1. Visual acuity [1 hour, 4 hours, 8 hours, and 1 week from baseline measurement]

      Measure distance and near visual acuity at baseline and re-measure after intervention of atropine 0.01% and atropine 0.1% for any changes

    2. Axial length [1 hour, 4 hours, 8 hours, and 1 week from baseline measurement]

      Measure axial length at baseline and compare to changes after intervention of atropine 0.01% and atropine 0.1%

    3. Lens thickness [1 hour, 4 hours, 8 hours, and 1 week from baseline measurement]

      Measure lens thickness at baseline and compare to changes after intervention of atropine 0.01% and atropine 0.1%

    4. Anterior chamber depth [1 hour, 4 hours, 8 hours, and 1 week from baseline measurement]

      Measure anterior chamber depth at baseline and compare to changes after intervention of atropine 0.01% and atropine 0.1%

    5. Quality of Vision (QoV) Questionnaire [1 hour, 4 hours, 8 hours, and 1 week from baseline measurement]

      The questionnaire is a Rasch-tested, linear-scaled, 30-item instrument on three scales providing a QoV score in terms of symptom frequency, severity, and bothersome. There are four options of increasing severity of symptoms from none, mild, moderate, and to severe for each item. The use of Rasch analysis turns the original questionnaire responses (raw ordinal data) into continuous interval data, providing a linear measurement; it is on a linear interval scale.

    6. Tear break up time (TBUT) [Baseline and 1 week from baseline measurement]

      Sodium fluorescein dye is added to the eye and the tear film is observed under the slit lamp while the patient avoids blinking until tiny dry spots develop; compare any differences between baseline and after one week of atropine use

    7. Schirmer strip test [Baseline and 1 week from baseline measurement]

      Measure amount of tear production; compare value at baseline to values after 1 week of atropine use to determine if tear production is affected with atropine use

    8. Ocular Surface Disease Index (OSDI) [Baseline and 1 week from baseline measurement]

      This is a 12-item questionnaire with 5 options from 0 to 5 (with 0 indicating none of the time, and increases to 5 indicating all of the time). The sum of the scores across the 12 items are totaled, and inputted into a formula to generate a sliding scale of the disease condition. The scale ranges from 0 to 100, with higher scores representing greater disability of the disease condition. This questionnaire will be completed at baseline and after 1 week of atropine use to compare for any differences.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 35 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Aged between 18 - 35 years

    • Good general and ocular health

    • Soft contact lens wearers to cease lens wear for at least 24 hours

    • No previous rigid gas permeable lens wear

    • Not taking monoamine oxidase inhibitors (MAOIs) and are not pregnant

    Exclusion Criteria:

    • History of ocular surgery, including refractive surgery

    • Use of ocular medications

    • Amblyopia

    • Conditions where topical atropine is contraindicated

    • Any eye or systemic disease that affect vision or refractive error

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 SUNY College of Optometry New York New York United States 10036

    Sponsors and Collaborators

    • State University of New York College of Optometry

    Investigators

    • Principal Investigator: Alexandra Benavente-Perez, PhD, State University of New York College of Optometry

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Franklin Bui, Co-principal investigator, State University of New York College of Optometry
    ClinicalTrials.gov Identifier:
    NCT03544827
    Other Study ID Numbers:
    • 1168531-2
    First Posted:
    Jun 4, 2018
    Last Update Posted:
    Feb 15, 2019
    Last Verified:
    Feb 1, 2019
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Franklin Bui, Co-principal investigator, State University of New York College of Optometry
    Atropine
    Additional relevant MeSH terms:
    Myopia
    Atropine

    Study Results

    No Results Posted as of Feb 15, 2019