CITT 2008.

Study characteristics
Methods	Study design: RCT Number randomized: 221 (54 assigned to home‐based pencil push‐ups (HBPP); 53 assigned to home‐based computer vergence/accommodative therapy and pencil push‐ups (HBCVAT+); 60 assigned to office‐based vergence/accommodative therapy with home reinforcement (OBVAT); 54 assigned to office‐based placebo therapy with home reinforcement (OBPT)) Unit of randomization: individual participant (convergence insufficiency is a binocular vision disorder) Number analyzed: 219 (99%) (53 of 54 assigned to HBPP; 52 of 53 assigned HBCVAT+; 59 of 60 assigned to OBVAT; 54 of 54 assigned to OBPT) Number of centers: 9 Date of first enrolment: July 2005 Length of follow‐up: planned: 12 weeks after initiation of treatment; actual: 12 weeks after initiation of treatment Sample size estimation: all sample size calculations were performed using PASS 2000 software and assuming a 2‐sided test with 90% power. For a given outcome measure, the common standard deviation (SD) obtained from the CITT pilot study was used as an estimate of variability. To control for multiple comparisons (4 groups, with 2 compared at a time [6 pair‐wise comparisons]), the α level used for determining sample size was set at 0.0083 (0.05/6). The sample size of 52 children per group was based on the required sample size for the 3 outcome variables and adjusted for a 10% loss to follow‐up.
Participants	Country of recruitment: United States Mean age: 11.9 ± 2.2 (SD) years in the HBPP group; 11.6 ± 2.3 (SD) years in the HBCVAT+ group; 12.0 ± 2.6 (SD) years in the OBVAT group; 11.8 ± 2.2 (SD) years in the OBPT group Sex: 50% were female in the HBPP group; 58% were female in the HBCVAT+ group; 68% were female in the OBVAT group; 59% were female in the OBPT group Key inclusion criteria: aged 9 to 17 years; exodeviation at near of at least 4 prism diopters greater than at far; receded near point of convergence (NPC) break (≥ 6 cm); insufficient positive fusional vergence at near (i.e., failing Sheard's criterion or < 15 Δ break on PFV); Convergence Insufficiency Symptom Survey (CISS) score ≥ 16; best‐corrected visual acuity of 20/25 or better in both eyes at distance and near; willingness to wear eyeglasses or contact lenses to correct refractive error, if necessary; appreciation of at least 500 seconds of arc on the forms part of the Randot Stereotest. Key exclusion criteria: convergence insufficiency previously treated with pencil push‐up therapy (> 2 weeks of treatment), home‐ or office‐based vergence/accommodative therapy; amblyopia; constant strabismus; history of strabismus surgery; necessary refractive error correction worn for at least 2 weeks prior to eligibility determination; prior refractive surgery; vertical heterophoria > 1 Δ; systemic diseases known to affect accommodation, vergence and ocular motility; accommodative amplitude < 5 D in either eye as measured by the Donders' push‐up method; manifest or latent nystagmus; developmental disability, mental retardation, attention‐deficit/hyperactivity disorder, or a learning disability; family or household member or sibling already enrolled in the CITT; family or household member of an eye care professional, ophthalmic technician, ophthalmology or optometry resident, or optometry student; convergence insufficiency secondary to acquired brain injury or any other neurological disorder.
Interventions	Intervention regimen #1: home‐based pencil push‐ups The pencil push‐ups procedure involved using a pencil with 20/60 reduced Snellen letters and a white index card placed in the background to provide a suppression check by using physiological diplopia awareness. The goal of the procedure was to move the pencil to within 2 to 3 cm of the brow, just above the nose on each push‐up while trying to keep the target single and clear. Patients were instructed to perform the pencil push‐ups procedure 15 minutes per day, 5 days per week. They maintained home therapy logs, recording the closest distance that they could maintain fusion after each 5 minutes of therapy. Intervention regimen #2: home‐based computer vergence/accommodative therapy and pencil push‐ups Patients in this group were taught to perform the pencil push‐up procedure as well as procedures on the Home Therapy System/Computerized Vergence System (HTS/CVS) computer software system (Computer Orthoptics, Gold Canyon, Arizona). Using this program, they performed fusional vergence and accommodative therapy procedures, including vergence base‐in, vergence base‐out, autoslide vergence, and jump ductions vergence programs using random‐dot stereopsis targets. The accommodative rock program was used for accommodative therapy. Much like a clinician would do at each follow‐up visit, this computer program automatically modified the therapy program after each session based on the patient’s performance. Patients were instructed to do pencil push‐ups 5 minutes per day, 5 days per week, and the HTS software program for 15 minutes per day, 5 days per week, and to save their data on a disk provided by the study and to bring the disk to each follow‐up visit. Intervention regimen #3: office‐based vergence/accommodative therapy with home reinforcement The OBVAT group received a weekly 60‐minute in‐office therapy visit with additional prescribed procedures to be performed at home for 15 minutes a day, 5 days per week. The therapy procedures are described in detail elsewhere (CITT 2008). At each office‐based therapy session, the patient performed 4 to 5 procedures with constant supervision and guidance from the therapist. There were no diagnostic tests performed during these sessions. The therapist followed a detailed and specific protocol from the CITT manual of procedures (http://optometry.osu.edu/research/CITT/4363.cfm); this document describes each procedure, amount of time procedure was performed, expected performance, and criteria for ending the procedure and advancing to a more difficult level. Intervention regimen #4: office‐based placebo therapy with home reinforcement Patients in the OBPT group received therapy during a weekly 60‐minute office visit and were prescribed procedures to be performed at home for 15 minutes per day, 5 days per week. The placebo therapy program consisted of 16 in‐office therapy procedures and 4 home therapy procedures, which were designed to look like real vergence/accommodative therapy procedures yet not to stimulate vergence, accommodation, or fine saccadic eye movement skills beyond normal daily visual activities. The therapist followed a detailed protocol from the CITT manual of procedures. Five procedures were performed during each office therapy visit and 2 procedures were assigned for home therapy each week. Objectives and goals were established for each placebo procedure to simulate real therapy. For motivational purposes, the therapist told the patient the objective of each procedure before beginning the technique.
Outcomes	Primary outcome: convergence insufficiency symptoms measured using Convergence Insufficiency Symptom Survey V‐15 after 12 weeks of therapy. The CI symptoms was also measured at baseline, 4 and 8 weeks of therapy. Key secondary outcomes: near point of convergence, and positive fusional vergence at near. The secondary outcomes were measured at baseline, 4, 8 and 12 weeks of therapy. No harms were reported.
Notes	Funding sources: National Eye Insititute, National Insitutes of Health, Bethesda, Maryland, USA. Subgroup analyses: none reported Trial registration: NCT00338611
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization was achieved using a secure web site created and managed by the data coordinating center. The web site generated the patient’s group assignment and assigned the patient a unique study identification number using a pre‐determined list generated by the data coordinating center. The randomization algorithm assigned patients to the four treatment groups with equal probability using a randomized permuted block design so investigators could not predict the sequence of treatment assignments. To ensure approximately equal numbers of patients in each treatment arm, randomization was performed separately for each clinical site.
Allocation concealment (selection bias)	Low risk	Access to the list was limited to the programmer and principal investigator of the data coordinating center (personal communication with the lead investigator).
Blinding (performance bias and detection bias) Primary outcome	Low risk	The examiners responsible for obtaining the outcome measures were masked to patient treatment assignment.  None of the examiners felt that they could identify the patients’ group assignment at the 4 or 8 week masked examinations, and only one examiner felt that he could identify the group assignment at outcome. One third of the examiners responded that their patient was assigned to the OBVAT group, 24% responded that he/she was assigned to HBCVAT+, 21% said their patient was assigned to HBPP, and 21% said their patient was assigned to the OBPT group. Examiners, when asked to guess, were correct in identifying the patient’s group assignment only 34% of the time, which is less than is expected by chance. There was low agreement between the actual group assignment and the examiner’s guess of assigned treatment group (0.11, 95% confidence interval, 0.04 to 0.20).
Blinding (performance bias and detection bias) Secondary outcomes	Low risk	See above.
Incomplete outcome data (attrition bias) Primary outcome	Unclear risk	"Statistical analyses techniques were employed which allowed for incomplete data. No imputation or sensitivity analyses were performed (personal communication with the lead investigator)".
Incomplete outcome data (attrition bias) Secondary outcomes	Unclear risk	See above.
Selective reporting (reporting bias)	Low risk	All outcomes listed in the study protocol were reported.