SAS1: A Prospective Observational Study of Adult Strabismus

• Sponsor: Jaeb Center for Health Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT02510040
• Collaborator: Pediatric Eye Disease Investigator Group (Other), National Eye Institute (NEI) (NIH)
• Enrollment: 217
• Location: 1
• Actual Duration (Months): 41.5
• Patients Per Site Per Month: 5.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Convergence Insufficiency; Divergence Insufficiency; Hypertropia	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 Design

• Study Type: Observational
• Actual Enrollment: 217 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Prospective Observational Study of Adult Strabismus
• Actual Study Start Date: Aug 17, 2015
• Actual Primary Completion Date: Dec 31, 2017
• Actual Study Completion Date: Jan 31, 2019

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Symptom Success at 10 Weeks [10 weeks after enrollment]

   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.

2. Number of Participants With Symptom Success at 12 Months [12 months after enrollment]

   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.

Secondary Outcome Measures

1. Mean of Near Point of Convergence in Convergence Insufficiency Group [12 months after enrollment]

   Near point of convergence (convergence insufficiency group only).

2. Mean Positive Fusional Vergence in Convergence Insufficiency Group [12 months after enrollment]

   Positive fusional vergence (convergence insufficiency group only).

3. Adult Strabismus 20 Questionnaire Score (DI) [12 months after enrollment]

   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)

4. Mean Convergence Insufficiency Symptom Survey Score [12 months after enrollment]

   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).

5. Adult Strabismus 20 Questionnaire Score (CI) [12 months after enrollment]

   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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Earl R. Crouch, III	Norfolk	Virginia	United States	23502-3942

Sponsors and Collaborators

• Jaeb Center for Health Research
• Pediatric Eye Disease Investigator Group
• National Eye Institute (NEI)

Investigators

• Study Chair: Earl R Crouch, III, MD, Virginia Pediatric Eye Center

Study Documents (Full-Text)

• Study Protocol - Apr 11, 2016
• Statistical Analysis Plan - Jun 4, 2020
• Informed Consent Form - Aug 10, 2015

More Information

Additional Information:

• PEDIG Public Website

Publications

None provided.

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT02510040
• Other Study ID Numbers: SAS1; 2U10EY011751
• First Posted: Jul 28, 2015
• Last Update Posted: Feb 9, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Jaeb Center for Health Research: Convergence Insufficiency; Divergence Insufficiency; Small-angle Hypertropia; Strabismus
• Additional relevant MeSH terms: Strabismus; Ocular Motility Disorders; Botulinum Toxins

Study Results

Participant Flow

Arm/Group Title	Convergence Insufficiency	Divergence Insufficiency	Small-angle Hypertropia
Arm/Group Description	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection
Period Title: Overall Study
STARTED	81	114	22
COMPLETED	63	111	21
NOT COMPLETED	18	3	1

Baseline Characteristics

Arm/Group Title	Convergence Insufficiency	Divergence Insufficiency	Small-angle Hypertropia	Total
Arm/Group Description	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection	Total of all reporting groups
Overall Participants	63	111	21	195
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.4 (18.6)	67.4 (13.7)	68.6 (13.0)	59.5 (19.4)
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	38.2	71.2	71.5	65.3
Sex: Female, Male (Count of Participants)
Female	48 76.2%	74 66.7%	10 47.6%	132 67.7%
Male	15 23.8%	37 33.3%	11 52.4%	63 32.3%
Race/Ethnicity, Customized (Count of Participants)
White	32 50.8%	107 96.4%	19 90.5%	158 81%
Non-white	31 49.2%	4 3.6%	2 9.5%	37 19%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Symptom Success at 10 Weeks
Description	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.
Time Frame	10 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Convergence Insufficiency	Divergence Insufficiency	Small-angle Hypertropia
Arm/Group Description	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection
Measure Participants	54	104	21
Count of Participants [Participants]	25 39.7%	91 82%	12 57.1%

2. Primary Outcome

Title	Number of Participants With Symptom Success at 12 Months
Description	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.
Time Frame	12 months after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Convergence Insufficiency	Divergence Insufficiency	Small-angle Hypertropia
Arm/Group Description	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection
Measure Participants	54	98	18
Count of Participants [Participants]	25 39.7%	73 65.8%	6 28.6%

3. Secondary Outcome

Title	Mean of Near Point of Convergence in Convergence Insufficiency Group
Description	Near point of convergence (convergence insufficiency group only).
Time Frame	12 months after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Convergence Insufficiency
Arm/Group Description	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection
Measure Participants	57
Mean (Standard Deviation) [centimeters]	14.1 (6.2)

4. Secondary Outcome

Title	Mean Positive Fusional Vergence in Convergence Insufficiency Group
Description	Positive fusional vergence (convergence insufficiency group only).
Time Frame	12 months after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Convergence Insufficiency
Arm/Group Description	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection
Measure Participants	57
Mean (Standard Deviation) [prism diopters]	11.6 (7.1)

5. Secondary Outcome

Title	Adult Strabismus 20 Questionnaire Score (DI)
Description	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)
Time Frame	12 months after enrollment

Outcome Measure Data

Analysis Population Description

This information was only collected and analyzed for the DI and CI arms. The HT arm cannot be reported since it was not collected. The CI arm data is currently being analyzed, and will be added to the record when analysis is complete, results are expected May 2021.

Arm/Group Title	Divergence Insufficiency
Arm/Group Description	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection
Measure Participants	111
General Function Score	62 (22)
Reading Function Score	71 (23)
Self Perception Score	87 (19)
Interaction Score	94 (11)

6. Secondary Outcome

Title	Mean Convergence Insufficiency Symptom Survey Score
Description	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).
Time Frame	12 months after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Convergence Insufficiency
Arm/Group Description	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection
Measure Participants	57
Mean (Standard Deviation) [points]	37.5 (9.1)

7. Secondary Outcome

Title	Adult Strabismus 20 Questionnaire Score (CI)
Description	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)
Time Frame	12 months after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Convergence Insufficiency
Arm/Group Description	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection
Measure Participants	57
General Function	55.7 (24.6)
Reading Function	43.9 (22.2)
Interaction	92.2 (14.7)
Self Perception	83.8 (22.6)

Adverse Events

Time Frame	Adverse event data was not collected since treatment was prescribed per usual standard of care.
Adverse Event Reporting Description	Per the study protocol (sections 4.4.1 and 4.5) Risks of Examination Procedures The procedures in this study are part of daily eye care practice in the United States and pose no known risks. Reporting of Adverse Events No treatments are being prescribed that are not part of usual care. Investigators will abide by local IRB reporting requirements.
Arm/Group Title	Convergence Insufficiency		Divergence Insufficiency		Small-angle Hypertropia
Arm/Group Description	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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection		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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection		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. Prism: Ground-in or Fresnel prism Orthoptic Exercises: Orthoptic exercises- fusion, convergence, divergence, and others, including computer-based therapy 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 Botox Injection: Botulinum toxin injection
All Cause Mortality
	Convergence Insufficiency		Divergence Insufficiency		Small-angle Hypertropia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Convergence Insufficiency		Divergence Insufficiency		Small-angle Hypertropia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Convergence Insufficiency		Divergence Insufficiency		Small-angle Hypertropia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.