CITT‐ART 2019.

Study characteristics
Methods	Study design: RCT Number randomized: 311 (206 assigned to 16 weeks of office‐based vergence/accommodative therapy (OBVAT); 104 assigned to 16 weeks of office‐based placebo therapy (OBPT); one participant was determined ineligible after randomization) Unit of randomization: individual participant (convergence insufficiency is a binocular vision disorder) Number analyzed: 302 (97%) (198 of 206 assigned to OBVAT; 104 of 104 assigned OBPT) Number of centers: 9 Date of first enrolment: September 2014 Length of follow‐up: planned: 16 weeks after initiation of treatment; actual: 16 weeks after initiation of treatment Sample size estimation:The CITT‐ART's pre‐planned sample size of 324 participants (216 in the OBVAT group and 108 in the OBPT group) was chosen to provide sufficient power for the trial's primary aim of determining whether treatment improved reading comprehension. This sample size provided > 95% power with a two‐sided type I error rate of 5% to detect treatment group differences in near point of convergence of ≥ 4 cm, CISS score of ≥ 10 points, positive fusional vergence of ≥ 10 Δ, and vergence facility of ≥ 3 cpm.
Participants	Country of recruitment: United States Mean age: 10.8 ±1.5 (SD) years in the OBVAT group; 10.9 ± 1.4 (SD) years in the OBPT group Sex: 58% were female in the OBVAT group; 46% were female in the OBPT group Key inclusion criteria: Age 9 to 14 y; Grades 3 to 8; CISS score ≥ 16; Exophoria at near (40 cm) at least 4 Δ greater than at far (4 m); Receded near point of convergence of ≥ 6‐cm break; Insufficient positive fusional vergence at near (40 cm; i.e., failing Sheard's criterion or positive fusional vergence ≤ 15 Δ BO break); Best‐corrected distance (4 m) and near visual acuity (40 cm) of 20/25 or better in each eye; Random‐dot stereopsis appreciation of 500 seconds of arc or better (40 cm); Willing to wear refractive correction for uncorrected refractive errors (based on cycloplegic refraction within prior 6 mo; correction must be worn for at least 2 weeks); Not wearing BI prism or a plus add at near for 2 weeks before study enrolment and for duration of study; The timing of enrolment must allow a participant to be attending school at both the baseline and the 16‐week outcome examination; English is primary language spoken at home, or the child is proficient in English as determined by the school; Parental permission to contact the child's teacher(s) for study purposes; The parent and child understand the protocol and are willing to accept randomization; The parent does not expect the child to start any new ADHD medicine or change the dose of any currently taken ADHD medicine while the child is being treated in the study. Key exclusion criteria: Constant strabismus at distance or near; Esophoria of ≥2Δ at distance; Vertical heterophoria ≥ 2 Δ at distance or near; ≥ 2‐line interocular difference in best‐corrected distance visual acuity; Monocular near point of accommodation > 20 cm (accommodative amplitude < 5 D) as measured by push‐up method; Manifest or latent nystagmus; Word reading subtest score < 80 on the WRAT‐4; KBIT‐2 matrices subtest score < 70; History of strabismus, intraocular, or refractive surgery; CI previously treated with any form of office‐based vergence/accommodative therapy or home‐based vergence therapy (e.g., computerized vergence therapy); CI associated with head trauma or known disease of the brain; Diseases known to affect accommodation, vergence, or ocular motility such as multiple sclerosis, Graves orbitopathy, myasthenia gravis, diabetes mellitus, Parkinson disease; Inability to comprehend and/or perform any study‐related test or procedure; Speech‐language disorder (e.g., stuttering) that would interfere with interpretation of digital recordings of reading tests; Significant hearing loss; Household member enrolled in the present CITT‐ART or treated within the past 6 mo with any form of office‐based vergence/accommodative therapy or home‐based vergence therapy (e.g., computerized vergence therapy); Household member is an eye care professional, ophthalmic technician, ophthalmology or optometry resident, or optometry student.
Interventions	A 16‐week program of weekly 60‐minute in‐office therapy specific to the assigned therapy (vergence/accommodative or placebo) group was administered by study‐certified optometrists, with four to five therapy procedures administered in the office and 15 minutes of daily home therapy prescribed for 5 days per week. Intervention regimen #1: OBVAT The OBVAT program was divided into 4 phases. Within each phase there are a number of categories such as gross convergence, vergence, and accommodation. Intervention regimen #2: OBPT The OBPT program comprised pre‐determined sequentially administered procedures designed to appear to be genuine therapy techniques but not to stimulate vergence, accommodation, or fine saccadic eye movements beyond normal daily visual activities.
Outcomes	Primary outcome: The change in the Wechsler Individual Achievement Test‐III (WIAT‐III) reading comprehension score as measured after the completion of 16 weeks of assigned treatment (OBVAT or OBPT) . Key secondary outcomes: change in the near point of convergence from baseline to 16 weeks; change in positive fusional vergence from baseline to 16 weeks; change in the CISS score from baseline to 16 weeks; composite outcome measures. A successful outcome was a score of < 16 on the CISS, a normal NPC (6 cm), and a normal PFV (15 and passing the Sheard’s criterion). Improved was defined as a score of < 16 or a 10‐point decrease in the CISS score, and at least 1 of the following: normal NPC, an improvement in NPC of more than 4 cm, normal PFV, or an increase in PFV of more than 10 Δ. No harms were reported.
Notes	Funding sources: National Eye Insititute, National Insitutes of Health, Bethesda, Maryland, USA. Subgroup analyses: none reported Trial registration: NCT02207517
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Participants were randomly allocated using a permuted block (sizes of 3, 6, and 9) design stratified by site and parent reported attention‐deficit/hyperactivity disorder status (yes/no) in a 2:1 allocation ratio to office‐based vergence/accommodative therapy or office‐based placebo therapy (hereafter placebo therapy), respectively."
Allocation concealment (selection bias)	Low risk	See above
Blinding (performance bias and detection bias) Primary outcome	Low risk	Protocol‐specified follow‐up visits were conducted by study‐certified optometrists and ophthalmologists masked to participants' treatment group after 4, 8, 12, and 16 weeks of therapy. Examiners were asked if they became unmasked to the participant's treatment group after each examination, and participants were asked upon completion of their 16‐week therapy program whether they thought they had received “real” vergence/accommodative therapy or placebo therapy. None of the examiners felt that they could identify the patients’ group assignment at the 4‐ or 8‐week masked examinations, and only 1 examiner felt that he could identify the group assignment at outcome.
Blinding (performance bias and detection bias) Secondary outcomes	Low risk	See above
Incomplete outcome data (attrition bias) Primary outcome	Low risk	"The 16‐week primary outcome visit was completed by 199 (96.6%) of the 206 participants in the vergence/accommodative group and by 100% of the 104 participants in the placebo group. Because only a few participants (n = 7) missed their 16‐week outcome visit, we believe that the probability of bias is low, and thus, an imputation analysis was not conducted."
Incomplete outcome data (attrition bias) Secondary outcomes	Low risk	See above.
Selective reporting (reporting bias)	Low risk	All prespecified outcomes were reported.