An Investigation of Topical Ophthalmic Low-Dose Atropine on Pupil Size and Accommodation

The goal of this clinical study is to learn about the short-term physiological effects of low-dose atropine in healthy volunteers. The study seeks to examine three questions related to low-dose topically applied ophthalmic atropine:

1. Does applying two drops of 0.01% atropine sulfate solution cause the same clinical effects as one drop of 0.02% atropine?
2. How quickly do the pupil responses and accommodative amplitudes recover following a dose of 0.01% atropine, 0.02% atropine, and 0.05% atropine?
3. Does applying a single drop of 0.02% atropine sulfate solution cause the same clinical effects in participants with light vs. dark iris colors? Participants will have their pupil size and accommodative status measured at appropriate intervals to answer the questions above.

Study Overview

• Status: Completed
• Conditions: Myopia
• Intervention / Treatment: Drug: Atropine 0.02% Ophthalmic Solution; Drug: Atropine 0.01% Ophthalmic Solution; Drug: Atropine 0.05% Ophthalmic Solution

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94720-2020
      • University of California, Berkeley

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects may be male or female, of any race, and between 18-40 years old at the time of screening.
2. Patients must have best spectacle corrected visual acuity of at least 0.10 logMAR (20/25) in each eye.
3. Subjects must be willing and able to apply eye drops to their non-dominant eye and to return for all scheduled follow-up visits.

Exclusion Criteria:

1. Subjects with any contraindication to atropine use (as listed on package insert). At the time of this submission, the only contraindication listed is: "Hypersensitivity or allergic reaction to any ingredient in formulation"
2. Subjects using monamine oxidase inhibitors (MAOIs). These are: Isocarboxazid (Marplan), Phenelzine (Nardil), Selegiline (Emsam), and Tranylcypromine (Parnate).
3. Subjects with a history of any of the following medical conditions: collagen vascular disease, autoimmune disease, immunodeficiency diseases, ocular herpes zoster or simplex, endocrine disorders (including, but not limited to active thyroid disorders and diabetes), lupus, and rheumatoid arthritis.
4. Subjects with a history of intraocular or corneal surgery (including cataract extraction), active ophthalmic disease or abnormality (including but not limited to, blepharitis, recurrent corneal erosion, dry eye syndrome, neovascularization >1mm from limbus), clinically significant lens opacity, clinical evidence of trauma (including scarring). This includes any patient with open-angle glaucoma, regardless of medication regimen or control. Additionally, any patient with an intra-ocular pressure (IOP) greater than 21 mm Hg at baseline is specifically excluded from eligibility. Subjects with narrow angles (less than Van Herick angle of 3) will also be excluded.
5. Subjects who are pregnant, planning to become pregnant or breastfeeding during the course of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single drop of 0.02% atropine sulfate solution; Participants received one drop of 0.02% atropine sulfate solution in one eye.	Drug: Atropine 0.02% Ophthalmic Solution; One drop of 0.02% atropine sulfate solution
Experimental: Two drops of 0.01% atropine sulfate solution; Participants received two drops of 0.01% atropine sulfate solution in one eye, spaced five minutes apart.	Drug: Atropine 0.01% Ophthalmic Solution; Two drops of 0.01% atropine sulfate solution
Other: observation of pupil responses; Subjects will be observed until pupils fully recover from a single dose of one of the atropine concentrations used.	Drug: Atropine 0.02% Ophthalmic Solution; One drop of 0.02% atropine sulfate solution; Drug: Atropine 0.01% Ophthalmic Solution; Two drops of 0.01% atropine sulfate solution; Drug: Atropine 0.05% Ophthalmic Solution; Atropine 0.05% Ophthalmic Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum pupil size	Dynamic pupil responses to a single pulse of light were measured 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours after instilling the drop(s). The smallest pupil size (maximum pupil restriction) was used as the primary outcome measure.	1-24 hours after drop application

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accommodative Amplitude	Subjective accommodative response was measured via the pull-away AA method.	1-24 hours after drop application

Collaborators and Investigators

• Sponsor: University of California, Berkeley
• Investigators: Principal Investigator: Sarah E Singh, OD, PhD, University of California, Berkeley

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2022
• Primary Completion (Actual): October 9, 2022
• Study Completion (Actual): October 9, 2022

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 30, 2026

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: atropine; myopia
• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Myopia; Pharmaceutical Solutions; Organic Chemicals; Heterocyclic Compounds; Pharmaceutical Preparations; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Alkaloids; Solutions; Specialty Uses of Chemicals; Aza Compounds; Heterocyclic Compounds, Bridged-Ring; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Atropine; Ophthalmic Solutions
• Other Study ID Numbers: 2021-09-14611

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD variables, including data dictionaries, will be available to other researchers upon request to the principal investigator and completion of a signed data sharing agreement.
• IPD Sharing Time Frame: As this study is being registered retroactively (and the study is complete), all data can be made available upon request at this time (March 2026).
• IPD Sharing Access Criteria: IPD can be accessed by emailing the PI who will make arrangements with appropriate UC Berkeley personnel to manage sharing.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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