The Effects of Low Dose Atropine on Choroidal Thickness

February 11, 2019 updated by: Franklin Bui, State University of New York College of Optometry

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10036
        • SUNY College of Optometry

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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 0.01%
  • Atropine 0.1%
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 0.01%
  • Atropine 0.1%

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Choroidal thickness
Time Frame: 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%
1 hour, 4 hours, 8 hours, and 1 week from baseline measurement

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual acuity
Time Frame: 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
1 hour, 4 hours, 8 hours, and 1 week from baseline measurement
Axial length
Time Frame: 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%
1 hour, 4 hours, 8 hours, and 1 week from baseline measurement
Lens thickness
Time Frame: 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%
1 hour, 4 hours, 8 hours, and 1 week from baseline measurement
Anterior chamber depth
Time Frame: 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%
1 hour, 4 hours, 8 hours, and 1 week from baseline measurement
Quality of Vision (QoV) Questionnaire
Time Frame: 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.
1 hour, 4 hours, 8 hours, and 1 week from baseline measurement
Tear break up time (TBUT)
Time Frame: 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
Baseline and 1 week from baseline measurement
Schirmer strip test
Time Frame: 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
Baseline and 1 week from baseline measurement
Ocular Surface Disease Index (OSDI)
Time Frame: 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.
Baseline and 1 week from baseline measurement

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

State University of New York College of Optometry

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 21, 2018

Primary Completion (Actual)

February 8, 2019

Study Completion (Actual)

February 8, 2019

Study Registration Dates

First Submitted

May 8, 2018

First Submitted That Met QC Criteria

May 31, 2018

First Posted (Actual)

June 4, 2018

Study Record Updates

Last Update Posted (Actual)

February 15, 2019

Last Update Submitted That Met QC Criteria

February 11, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1168531-2

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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