A Prospective Observational Study of Adult Strabismus (SAS1)

The purpose of this study is to describe clinical characteristics, treatments, and one-year outcomes of adults with convergence insufficiency, divergence insufficiency, or small angle hypertropia.

Study Overview

• Status: Completed
• Conditions: Convergence Insufficiency; Divergence Insufficiency; Hypertropia
• Intervention / Treatment: Device: Prism; Other: Orthoptic Exercises; Procedure: Eye Muscle Surgery; Procedure: Botox Injection

Detailed Description

The purpose of this study is to describe clinical characteristics, treatments, and one-year outcomes of adults with convergence insufficiency, divergence insufficiency, or small angle hypertropia. Treatment comparisons within the studied conditions will also be done to help develop future studies.

• Study Type: Observational
• Enrollment (Actual): 217

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Norfolk, Virginia, United States, 23502-3942
      • Earl R. Crouch, III

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Community Sample

Description

Eligibility Criteria for Convergence Insufficiency (CI) Group:

The following inclusion criteria must be met for the subject to be enrolled into the study:

• Adults ≥18 years of age (adult onset of CI not required)
• No strabismus surgery within the past 10 years
• CI Symptom Survey score ≥21 points
• Near exodeviation of ≥4∆ and at least 4∆ larger than at distance by PACT
• Distance exodeviation ≤15∆ by PACT
• Vertical deviation ≤2∆ at distance and near by PACT
• No constant exotropia at distance or near
• Reduced positive fusional vergence (PFV) at near (<20∆ or fails Sheard's criterion that the PFV measures less than twice the magnitude of the near phoria)
• Near point of convergence (NPC) of ≥6 cm break
• Visual acuity 20/50 or better in both eyes by ETDRS or Snellen
• No paralytic strabismus (e.g., 3rd, 4th, or 6th cranial nerve palsies, skew deviation, Duane syndrome)
• No restrictive strabismus (e.g., blowout fracture, thyroid eye disease, post scleral buckle, Brown syndrome)
• No monocular diplopia
• No paretic strabismus, thyroid eye disease, myasthenia gravis, chronic progressive external ophthalmoplegia, or eye movement abnormalities associated with known neurological disease. Patients with Parkinson's disease can be enrolled if non-paretic deviation.
• No inferior or superior oblique overaction defined as 2+ or greater
• Ability to fuse with prism in space (see section 2.4.1)
• Ability to understand and complete a survey
• Investigator is initiating treatment with prism, orthoptic exercises, botulinum toxin injection or surgery
• If initiating treatment with botulinum toxin or surgery, planned injection or surgery to be within 60 days of enrollment
• Single treatment modality is planned (e.g., no combined prism and orthoptic exercises)
• Treatment to be initiated has not been used within the past one year

Eligibility Criteria for Divergence Insufficiency (DI) Group:

The following inclusion criteria must be met for the subject to be enrolled into the study:

• Adults ≥18 years of age
• Adult-onset DI (at ≥18 years of age)
• No prior strabismus surgery
• Symptoms of diplopia at distance with a frequency of sometimes or worse in primary position (in current glasses if wearing glasses)
• Distance esodeviation of 2∆ to 30∆ and at least 50% larger than at near by PACT
• No more than 5∆ difference between right and left gaze by PACT
• No more than 10∆ difference between the primary position at distance and either upgaze or downgaze ≤10∆ by PACT
• Any coexisting vertical deviation must be less than distance esodeviation and ≤10∆ by PACT
• Visual acuity 20/50 or better in both eyes by ETDRS or Snellen
• No paralytic strabismus (e.g., 3rd, 4th, or 6th cranial nerve palsies, skew deviation, Duane syndrome)
• No restrictive strabismus (e.g., blowout fracture, thyroid eye disease, post scleral buckle, Brown syndrome)
• No monocular diplopia
• No paretic strabismus, thyroid eye disease, myasthenia gravis, chronic progressive external ophthalmoplegia, or eye movement abnormalities associated with known neurological disease. Patients with Parkinson's disease can be enrolled if non-paretic deviation
• No inferior or superior oblique overaction defined as 2+ or greater
• Ability to fuse with prism in space (see section 2.4.2)
• Ability to understand and complete a survey
• Investigator is initiating treatment with prism, orthoptic exercises, botulinum toxin injection or surgery
• If initiating treatment with botulinum toxin or surgery, planned injection or surgery to be within 60 days of enrollment
• Single treatment modality planned (e.g., no combined prism and orthoptic exercises)
• Treatment to be initiated has not been used within the past one year

Eligibility Criteria for Small-angle Hypertropia (HT) Group:

The following inclusion criteria must be met for the subject to be enrolled into the study:

• Adults ≥18 years of age
• Adult-onset HT (at ≥18 years of age)
• No prior strabismus surgery
• Symptoms of diplopia at distance or near with a frequency of sometimes or worse in primary or reading position (in current glasses if wearing glasses)
• Vertical deviation ≥1∆ to ≤10∆ at distance and near by PACT
• No more than 4∆ difference from the primary in any gaze position by PACT
• Any coexisting esodeviation must be less than the vertical deviation
• Any coexisting exodeviation ≤10∆ by PACT
• No convergence insufficiency as defined in section 2.2.1
• Visual acuity 20/50 or better in both eyes by ETDRS or Snellen
• No paralytic strabismus (e.g., 3rd, 4th, or 6th cranial nerve palsies, skew deviation, Duane syndrome)
• No restrictive strabismus (e.g., blowout fracture, thyroid eye disease, post scleral buckle, Brown syndrome)
• No monocular diplopia
• No paretic strabismus, thyroid eye disease, myasthenia gravis, chronic progressive external ophthalmoplegia, or eye movement abnormalities associated with known neurological disease. Patients with Parkinson's disease can be enrolled if non-paretic deviation.
• No inferior or superior oblique overaction defined as 2+ or greater
• Ability to fuse with prism in space (see section 2.4.3)
• Ability to understand and complete a survey
• Investigator is initiating treatment with prism, orthoptic exercises, botulinum toxin injection or surgery
• If initiating treatment with botulinum toxin or surgery, planned injection or surgery to be within 60 days of enrollment
• Single treatment modality planned (e.g., no combined prism and orthoptic exercises)
• Treatment to be initiated has not been used within the past one year

Exclusion Criteria for Convergence Insufficiency (CI) Group:

The following criteria exclude a subject from enrollment into the study:

• Strabismus surgery within the past 10 years
• CI Symptom Survey score ≥21 points
• Near exodeviation of ≤4∆ and at least 4∆ larger than at distance by PACT
• Distance exodeviation ≥15∆ by PACT
• Vertical deviation ≥2∆ at distance and near by PACT
• Constant exotropia at distance or near
• Near point of convergence (NPC) of ≤6 cm break
• Visual acuity worse than 20/50 either eye by ETDRS or Snellen
• Paralytic strabismus (e.g., 3rd, 4th, or 6th cranial nerve palsies, skew deviation, Duane syndrome)
• Restrictive strabismus (e.g., blowout fracture, thyroid eye disease, post scleral buckle, Brown syndrome)
• Monocular diplopia
• Paretic strabismus, thyroid eye disease, myasthenia gravis, chronic progressive external ophthalmoplegia, or eye movement abnormalities associated with known neurological disease. Patients with Parkinson's disease can be enrolled if non-paretic deviation.
• Inferior or superior oblique overaction defined as 2+ or greater
• Inability to fuse with prism in space (see section 2.4.1)
• Inability to understand and complete a survey
• Treatment to be initiated has already been used within the past one year

Exclusion Criteria for Divergence Insufficiency (DI) Group:

The following criteria exclude a subject from enrollment into the study:

• No adult-onset DI (at ≥18 years of age)
• Prior strabismus surgery
• Distance esodeviation outside the range of 2∆ to 30∆ and less than 50% larger than at near by PACT
• More than 5∆ difference between right and left gaze by PACT
• More than 10∆ difference between the primary position at distance
• Any coexisting vertical deviation more than distance esodeviation and ≥10∆ by PACT
• Visual acuity worse than 20/50 in either eye by ETDRS or Snellen
• Paralytic strabismus (e.g., 3rd, 4th, or 6th cranial nerve palsies, skew deviation, Duane syndrome)
• Restrictive strabismus (e.g., blowout fracture, thyroid eye disease, post scleral buckle, Brown syndrome)
• Monocular diplopia
• Paretic strabismus, thyroid eye disease, myasthenia gravis, chronic progressive external ophthalmoplegia, or eye movement abnormalities associated with known neurological disease.
• Inferior or superior oblique overaction defined as 2+ or greater
• Inability to fuse with prism in space (see section 2.4.2)
• Inability to understand and complete a survey
• Treatment to be initiated has already been used within the past one year

Exclusion Criteria for Small-angle Hypertropia (HT) Group:

The following criteria exclude a subject from enrollment into the study:

• No adult-onset HT (at ≥18 years of age)
• Prior strabismus surgery
• Vertical deviation ≤1∆ or ≥10∆ at distance and near by PACT
• More than 4∆ difference from the primary in any gaze position by PACT
• Coexisting esodeviation must not be less than the vertical deviation
• Coexisting exodeviation ≥10∆ by PACT
• Convergence insufficiency as defined in section 2.2.1
• Visual acuity worse than 20/50 in either eye by ETDRS or Snellen
• Paralytic strabismus (e.g., 3rd, 4th, or 6th cranial nerve palsies, skew deviation, Duane syndrome)
• Restrictive strabismus (e.g., blowout fracture, thyroid eye disease, post scleral buckle, Brown syndrome)
• Monocular diplopia
• Paretic strabismus, thyroid eye disease, myasthenia gravis, chronic progressive external ophthalmoplegia, or eye movement abnormalities associated with known neurological disease.
• Inferior or superior oblique overaction defined as 2+ or greater
• Inability to fuse with prism in space (see section 2.4.3)
• Inability to understand and complete a survey
• Treatment to be initiated has already been used within the past one year

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Convergence insufficiency; Eligible adults with convergence insufficiency can be treated with prism, orthoptic exercises, eye muscle surgery, or botox injection, per the investigator's usual clinical practice.	Device: Prism; Ground-in or Fresnel prism; Other: Orthoptic Exercises; Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy; Procedure: Eye Muscle Surgery; Bilateral medial rectus muscle resection surgery; Single medial rectus muscle resection surgery; Recess lateral rectus muscle resection medial rectus muscle surgery; Bilateral lateral rectus muscle recession surgery; Single lateral rectus muscle recession surgery; Bilateral lateral rectus muscle resection surgery; Single lateral rectus muscle resection surgery; Recess medial rectus muscle resection lateral rectus muscle surgery; Bilateral medial rectus muscle recession surgery; Single medial rectus muscle recession surgery; Vertical rectus muscle recession surgery; Vertical rectus muscle mini-tenotomy (snip) surgery; Procedure: Botox Injection; Botulinum toxin injection; Other Names: Botulinum toxin injection
Divergence insufficiency; Eligible adults with divergence insufficiency can be treated with prism, orthoptic exercises, eye muscle surgery, or botox injection, per the investigator's usual clinical practice.	Device: Prism; Ground-in or Fresnel prism; Other: Orthoptic Exercises; Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy; Procedure: Eye Muscle Surgery; Bilateral medial rectus muscle resection surgery; Single medial rectus muscle resection surgery; Recess lateral rectus muscle resection medial rectus muscle surgery; Bilateral lateral rectus muscle recession surgery; Single lateral rectus muscle recession surgery; Bilateral lateral rectus muscle resection surgery; Single lateral rectus muscle resection surgery; Recess medial rectus muscle resection lateral rectus muscle surgery; Bilateral medial rectus muscle recession surgery; Single medial rectus muscle recession surgery; Vertical rectus muscle recession surgery; Vertical rectus muscle mini-tenotomy (snip) surgery; Procedure: Botox Injection; Botulinum toxin injection; Other Names: Botulinum toxin injection
Small-angle hypertropia; Eligible adults with small-angle hypertropia can be treated with prism, orthoptic exercises, eye muscle surgery, or botox injection, per the investigator's usual clinical practice.	Device: Prism; Ground-in or Fresnel prism; Other: Orthoptic Exercises; Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy; Procedure: Eye Muscle Surgery; Bilateral medial rectus muscle resection surgery; Single medial rectus muscle resection surgery; Recess lateral rectus muscle resection medial rectus muscle surgery; Bilateral lateral rectus muscle recession surgery; Single lateral rectus muscle recession surgery; Bilateral lateral rectus muscle resection surgery; Single lateral rectus muscle resection surgery; Recess medial rectus muscle resection lateral rectus muscle surgery; Bilateral medial rectus muscle recession surgery; Single medial rectus muscle recession surgery; Vertical rectus muscle recession surgery; Vertical rectus muscle mini-tenotomy (snip) surgery; Procedure: Botox Injection; Botulinum toxin injection; Other Names: Botulinum toxin injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Symptom Success at 10 Weeks	In the convergence insufficiency group, the primary outcome will be symptom success at the 10-week and 12-month visit, defined as improvement of CI Symptom Survey (CISS) score of at least 9 points and an outcome score of <21 points. In the divergence insufficiency group, the primary outcome will be symptom success at the 10-week and 12-month visit, defined as diplopia "rarely" or "never" in primary position at distance on the diplopia questionnaire. In the small-angle hypertropia group, the primary outcome will be symptom success at the 10-week and 12-month visit, defined as diplopia "rarely" or "never" both in primary position at distance and in reading position on the diplopia questionnaire.	10 weeks after enrollment
Number of Participants With Symptom Success at 12 Months	In the convergence insufficiency group, the primary outcome will be symptom success at the 10-week and 12-month visit, defined as improvement of CI Symptom Survey (CISS) score of at least 9 points and an outcome score of <21 points. In the divergence insufficiency group, the primary outcome will be symptom success at the 10-week and 12-month visit, defined as diplopia "rarely" or "never" in primary position at distance on the diplopia questionnaire. In the small-angle hypertropia group, the primary outcome will be symptom success at the 10-week and 12-month visit, defined as diplopia "rarely" or "never" both in primary position at distance and in reading position on the diplopia questionnaire.	12 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean of Near Point of Convergence in Convergence Insufficiency Group	Near point of convergence (convergence insufficiency group only).	12 months after enrollment
Mean Positive Fusional Vergence in Convergence Insufficiency Group	Positive fusional vergence (convergence insufficiency group only).	12 months after enrollment
Adult Strabismus 20 Questionnaire Score (DI)	Adult Strabismus Quality of Life Questionnaire (AS-20) For AS-20, scores are reported for the following subscales. A total score will not be reported.; Self-perception score; Interaction score; Reading function score; General function score Values for each subscale range from 0 to 100. 0 indicates poor quality of life (the patient reported "always" for all questions) and 100 represents good quality or life (patient reported "never" for all questions)	12 months after enrollment
Mean Convergence Insufficiency Symptom Survey Score	Mean Convergence Insufficiency Symptom Survey Score (convergence insufficiency group only) For CISS, the range is from 0 (having no symptoms of CI) to 60 (always showing all symptoms of CI).	12 months after enrollment
Adult Strabismus 20 Questionnaire Score (CI)	Adult Strabismus Quality of Life Questionnaire (AS-20) For AS-20, scores are reported for the following subscales. A total score will not be reported. Self-perception score Interaction score Reading function score General function score Values for each subscale range from 0 to 100. 0 indicates poor quality of life (the patient reported "always" for all questions) and 100 represents good quality or life (patient reported "never" for all questions)	12 months after enrollment

Collaborators and Investigators

• Sponsor: Jaeb Center for Health Research
• Collaborators: National Eye Institute (NEI); Pediatric Eye Disease Investigator Group
• Investigators: Study Chair: Earl R Crouch, III, MD, Virginia Pediatric Eye Center

Publications and helpful links

General Publications

• Crouch ER, Dean TW, Kraker RT, Miller AM, Kraus CL, Gunton KB, Repka MX, Marsh JD, Del Monte MA, Luke PA, Peragallo JH, Lee KA, Wheeler MB, Daley TJ, Wallace DK, Cotter SA, Holmes JM; Pediatric Eye Disease Investigator Group. A prospective study of treatments for adult-onset divergence insufficiency-type esotropia. J AAPOS. 2021 Aug;25(4):203.e1-203.e11. doi: 10.1016/j.jaapos.2021.02.014. Epub 2021 Jul 13.
• Lorenzana IJ, Leske DA, Hatt SR, Dean TW, Jenewein EC, Dagi LR, Beal CJ, Pang Y, Retnasothie DV, Esposito CA, Erzurum SA, Aldrich AE, Crouch ER, Li Z, Kraker RT, Holmes JM, Cotter SA; Pediatric Eye Disease Investigator Group; Pediatric Eye Disease Investigator Group. Relationships among Clinical Factors and Patient-reported Outcome Measures in Adults with Convergence Insufficiency. Optom Vis Sci. 2022 Sep 1;99(9):692-701. doi: 10.1097/OPX.0000000000001929. Epub 2022 Aug 2.

Helpful Links

• PEDIG Public Website

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2015
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): January 31, 2019

Study Registration Dates

• First Submitted: July 24, 2015
• First Submitted That Met QC Criteria: July 24, 2015
• First Posted (Estimated): July 28, 2015

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Strabismus; Convergence Insufficiency; Divergence Insufficiency; Small-angle Hypertropia
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Cranial Nerve Diseases; Strabismus; Ocular Motility Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Botulinum Toxins
• Other Study ID Numbers: SAS1; 2U10EY011751 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with the NIH data sharing policy, a de-identified database is placed in the public domain on the Pediatric Eye Disease Investigator Group (PEDIG) public website after the completion of each protocol and publication of the primary manuscript.
• IPD Sharing Time Frame: After completion of the protocol and publication of the primary manuscript, the data will be made available for the duration of the grant and any future grants.
• IPD Sharing Access Criteria: public
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF