Convergence Insufficiency Neuro-mechanism in Adult Population Study Randomized Clinical Trial: Clinical Outcome Results

Abstract

SIGNIFICANCE 

These data confirm the effectiveness of office-based vergence/accommodative therapy for improving the near point of convergence and positive fusional vergence in young adults with symptomatic convergence insufficiency within a double-masked longitudinal randomized clinical trial.

PURPOSE 

This study aimed to report changes in clinical signs and symptoms of convergence insufficiency from a randomized clinical trial evaluating the effectiveness of office-based vergence/accommodative therapy for young adults with symptomatic convergence insufficiency.

METHODS 

In this double-masked, randomized clinical trial, convergence insufficiency patients (n = 50; average age, 21 ± 3 years; range, 18 to 32 years) were randomized to either office-based vergence/accommodative therapy or office-based placebo therapy. Improvements in (1) near point of convergence, (2) positive fusional vergence, and (3) self-reported symptoms (Convergence Insufficiency Symptom Survey [CISS] score) were evaluated after twelve 1-hour sessions of treatment within the office comparing the results from the vergence/accommodative therapy and the placebo therapy groups.

RESULTS 

The mean near point of convergence improved by 6.0 and 3.1 cm in the vergence/accommodative and placebo therapy groups, respectively (mean difference of −2.9 cm; 95% confidence interval [CI], −4.6 to −1.0 cm; P < .01). The mean positive fusional vergence increased by 17.3 and 7.4Δ in the vergence/accommodative and placebo therapy groups, respectively (mean difference of 9.9Δ; 95% CI, 4.9 to 16.0Δ; P < .001). The mean CISS score improved by 12.4 and 10.1 points in the vergence/accommodative and placebo therapy groups, respectively (mean difference of 2.3 points; 95% CI, −8.3 to +4.6 points; P = .56).

CONCLUSIONS 

Our results demonstrate that office-based vergence/accommodative therapy is effective for improving the near point of convergence and positive fusional vergence in young adults with symptomatic convergence insufficiency. However, given that both treatment groups had a similar reduction in self-reported symptoms, we recommend that the CISS be revised if it is to be used as an outcome measure in future studies of convergence insufficiency.

Multiple randomized clinical trials studying the effectiveness of nonsurgical treatments for convergence insufficiency in children have been published in recent years. These include studies of base-in prism for reading,¹ home-based pencil push-ups,^2–4 home-based computer vision therapy,^3,4 and office-based vergence/accommodative therapy.^2,4–6 There is a great deal of homogeneity in these studies of children regarding the age of the participants, eligibility criteria, therapy protocol, and outcome measures in the studies that included office-based vergence/accommodative therapy,^2,4,5 which facilitated the ability to analyze the combined data (578 participants) in a meta-analysis.⁷ Although three randomized clinical trials have been performed with the young adult population with symptomatic convergence insufficiency between 15 and 35 years of age, with an average age within each study in the early to late 20s,^8–10 these studies lack homogeneities regarding the age of the participants, eligibility criteria, therapy protocol, and outcome measures. Thus, there is a need for additional data on the effectiveness of office-based vergence/accommodative therapy in young adults with symptomatic convergence insufficiency.

We recently completed the Convergence Insufficiency Neuro-mechanism in Adult Population Study, which had the following specific aims: (1) to identify the underlying neural mechanism(s) that differ(s) at baseline between young adults with symptomatic convergence insufficiency and those with normal binocular vision and (2) to determine the underlying neural mechanism(s) that significantly change(s) after office-based vergence/accommodative therapy in young adults with symptomatic convergence insufficiency. As part of this second aim, we identified young adults with symptomatic convergence insufficiency and randomized them into either office-based vergence/accommodative therapy or office-based placebo therapy. Herein, we report the results of this sub-aim of the Convergence Insufficiency Neuro-mechanism in Adult Population Study, comparing the effectiveness of office-based vergence/accommodative therapy with that of office-based placebo therapy for improving clinical measures and symptoms in young adults with symptomatic convergence insufficiency. These data are an important contribution to the literature because of the limited information currently available for the adult population. The data related to the neural mechanism of office-based vergence/accommodative therapy are included in a separate article.

METHODS

The Convergence Insufficiency Neuro-mechanism in Adult Population Study was supported by the National Eye Institute of the National Institutes of Health and conducted according to the tenets of the Declaration of Helsinki. The institutional review board of the New Jersey Institute of Technology and Rutgers University approved the protocol and the informed consent forms. Each study participant gave written informed consent. The study is registered at ClinicalTrials.gov as Neural Mechanism of Vision Therapy for Patients with Convergence Insufficiency: NCT03593031. The Convergence Insufficiency Neuro-mechanism in Adult Population Study is a longitudinal double-masked randomized clinical trial study. The complete protocol is available in a previous publication.^11,12 Herein, we summarize the most relevant portions of the protocol.

Participant Selection

The study included adults 18 to 35 years old with symptomatic convergence insufficiency, recruited from the student body of the surrounding universities within Newark, NJ (Fig. 1). Flyers and other announcements were used to make students aware of this clinical study. Students interested in the study were asked to first complete the Convergence Insufficiency Symptom Survey (CISS). If the symptom score was ≥21, then the individual was given information on the study, and if after review they decided to continue, an enrollment visit was scheduled. This enrollment visit was designed to determine if the potential participant had symptomatic convergence insufficiency and to gather baseline data including the CISS.^13,14 Symptomatic convergence insufficiency was defined as (1) a near exodeviation that is at least 4∆ greater than at distance fixation (as measured with the prism and an alternate cover test), (2) a receded (≥6 cm) near point of convergence, (3) insufficient positive fusional vergence (i.e., convergence amplitudes) at near defined as failing Sheard's criterion¹⁵ (base-out blur [break if no blur] less than twice the near phoria) or minimum positive fusional vergence at near of ≤15∆ base-out break, and (4) a score of ≥21 on the CISS. Other eligibility criteria included best-corrected visual acuity at distance and near of 20/25 and wearing appropriate refractive correction (spectacles or contact lenses) for at least 2 weeks before study enrollment. Exclusion criteria included anisometropia of greater than 1.5 D, other binocular vergence dysfunctions such as strabismus, other neurological disease(s) such as Parkinson disease and Huntington disease, or a history of concussion. The full eligibility and exclusion criteria are available in a previous publication.¹¹

FIGURE 1: CONSORT flowchart of the study.

Enrollment/Randomization

The near point of convergence and amplitude of accommodation were measured with the Astron International (ACR/21) Accommodative Rule (single column of letters, 20/30 equivalent at 40 cm). The near point of convergence was measured three times, and the average value was used to determine eligibility and later to assess the treatment effect. Amplitude of accommodation was measured monocularly for the right eye where the left eye was occluded, and the participants viewed the 20/30 single column of letters. Then, the left eye amplitude of accommodation was measured where the right eye was occluded. The column of letters was slowly brought toward the participant until he/she reported the first perception of blur for the left eye, and this process was repeated for the right eye.

Positive fusional vergence (blur, break, and recovery) was measured with a horizontal prism bar (Gulden B-15 horizontal prism bar: 1 to 45∆; Gulden Ophthalmics, Elkins Park, PA) while the patient viewed a 20/30 size column of letters (Gulden Fixation Stick no. 15302) held at 40 cm. Positive fusional vergence was measured three times, and the mean of the three measures was used to determine eligibility. Vergence facility was recorded using a 12∆ base-out with 3∆ base-in prism on a rod. The participant would view the 20/30 column of letters (Gulden Fixation Stick no. 15302) 40 cm away along the participant's midline. The participant would report when he/she saw the visual target single and clear, and then the operator would change the prism. The number of cycles (viewing the base-out and then the base-in) of the prism was recorded within 1 minute. The examiner recorded if the participant had difficulty with the base-out, base-in, or both prisms. The instructional sets for each test were identical to those used in previous clinical trials.^2,4,5,8,16

If a patient was wearing glasses and no change in prescription was necessary, randomization into active or sham groups occurred immediately. If a significant uncorrected refractive error was present or a significant change in refractive correction was required, the patient was not eligible for the study. A significant refractive error or change in needed refractive correction was defined as 1.50 D hyperopia, 0.50 D myopia, 0.75 D astigmatism, 0.75 D anisometropia in spherical equivalent, or 1.50 D anisometropia in any meridian (based on noncycloplegic refraction). The activities of the participant before examination were not precisely known, and the time of day that the examination was conducted was not controlled.

Each participant was assigned to either office-based vergence/accommodative therapy (hereinafter vergence/accommodative therapy) or office-based placebo therapy (hereinafter placebo therapy) using a randomized vector with a 1:1 allocation ratio created by a random number generator within a custom MATLAB script (Natick, MA) in accordance with the CONSORT 2010 agreement.^17,18 The randomized vector was only accessible to the research coordinator; hence, the primary investigators were concealed from treatment assignment.

Treatment Protocols for Both Therapy Groups

All participants received office-based therapy administered by a trained therapist during a biweekly, 60-minute office visit, with additional procedures to be performed at home for 10 minutes a day, three times per week during the duration of the therapy. Home therapy was to be conducted on days when office-based therapy was not conducted. The objective was for participants to attend two 60-minute therapy sessions per week for 6 weeks. The home therapy was all computer based (HTS, visiontherapysolutions.net). The readily available HTS program was used for the vergence/accommodative therapy group, whereas the placebo group used a custom-designed HTS program. Although this custom-designed program looked similar, there was never any change in the vergence demand after correct or incorrect responses. For both treatment arms, the therapist followed a detailed protocol that described the proper treatment technique, amount of time the technique was to be done, expected performance, and the criteria required to advance to the next procedure in the treatment sequence as described in our prior publication.¹¹

Vergence/Accommodative Therapy

The office- and home-based procedures were designed to improve convergence amplitude, fusional vergence and facility, accommodative amplitude, and facility. The initial phase of therapy was designed to normalize accommodation amplitude and improve the near point of convergence and positive fusional vergence using ramp stimuli. In phase 2 of the treatment program, step vergence demand was incorporated into the therapy along with procedures designed to improve negative fusional vergence. The objectives of the final phase were to develop the vergence facility and to integrate vergence procedures with version eye movements. The therapy techniques included the use of vectograms, aperture rule, eccentric circles, HTS computer orthoptics, and monocular accommodative procedures using loose lenses. The level of difficulty gradually increased throughout the 12-session sequence. The specific procedures used are described in detail elsewhere.¹¹

Placebo Therapy

The procedures for placebo therapy were designed to simulate real-vision-therapy procedures without the expectation of affecting vergence, accommodation, or saccadic function. Examples included stereograms presented monocularly to simulate vergence therapy, computer vergence therapy with no vergence changes, and using a monocular prism (instead of plus and minus lenses) to simulate accommodative treatment. The procedures used were similar to those described in previous clinical trials performed by the Convergence Insufficiency Treatment Trial Investigator group.^5,19–21

Follow-up Examinations and Test Procedures

The primary outcome examination was scheduled after a participant completed 12 hours of office-based therapy with a frequency of about two sessions per week. This typically occurred 6 to 8 weeks after enrollment. At the outcome visit, the examiner, who was masked to the patient's treatment group, administered the CISS, cover testing at distance and near, near point of convergence, positive fusional vergence at near, accommodative amplitude, and near vergence facility. The study ended for all participants after completion of the primary outcome visit.

Masking of Participants and Examiner

The examiner who performed the outcome examination was masked to the treatment assignment and baseline data to avoid bias. Because experienced therapists provided the treatments, it was not feasible to mask them to their patients' assigned treatment groups. The participants, however, were masked to the treatment assignment. At the end of treatment, all participants were asked whether they thought they were in real or placebo therapy and rate their response using a 5-point Likert scale, stating whether they were very sure, pretty sure, a little sure, somewhat sure, or not sure at all of their response.

Adherence to the Treatment Protocol

Because the home therapy was computer based, data about the number of sessions performed, time spent, and performance achieved were available to the research team and could be accessed through the therapy software. Participants for both groups were encouraged to perform their home-based computer therapy during each office-based session. Home-based therapy patient adherence was calculated by dividing the number of sessions completed at home by the maximum number of at-home sessions prescribed (3 sessions per week for 6 weeks, which is 18 home sessions).

Statistical Methods

The sample size was calculated using paired t tests with equal variance for convergence insufficiency participants from both the vergence/accommodative therapy and placebo therapy groups, using an intent-to-treat analysis. We used data from a previous Convergence Insufficiency Treatment Trial Investigator study to define clinically meaningful differences for CISS, near point of convergence, and positive fusional vergence.² Based on the results of previous studies, a difference of 8 points on the CISS led to a Cohen d effect size of 0.94, which is about 1 standard deviation. From the same study, 4 cm for the near point of convergence and 10Δ for positive fusional vergence were considered clinically meaningful.^2,5 This gives standard deviations of the difference (vergence/accommodative therapy minus placebo therapy) to be 19 points, 2 cm, and 19Δ, respectively. Assuming an 80% power and an α of 0.05, results in the number of participants needed to be 25, 4, and 25, respectively, as described in prior studies.^5,19,20 Hence, 25 samples were studied for each cohort. All statistical calculations were computed using IBM SPSS Statistics version 20 (IBM, Armonk, NY).

Outcome Measures

The main analyses were the between-group differences using an unpaired t test and a two-sided, 95% confidence interval of the change in the near point of convergence, positive fusional vergence, and the CISS score from baseline to the outcome visit calculated using an intent-to-treat analysis. A change of 1 standard deviation or greater was the criterion used in this study to determine whether there was a clinically meaningful change in each of the outcome measures. To be consistent with previous clinical trials by the Convergence Insufficiency Treatment Trial Investigator group,^5,10,19–22 we also evaluated four other pre-planned outcomes of success (Table 1) using χ² tests to determine if the proportions of successful outcomes differed between the two treatment groups. In addition, amplitude of accommodation and vergence facility measures were included within the results but were not classified as main outcome measures.

TABLE 1 - Success criteria

Outcome		Criterion 1: normal or improved	Criterion 2: normal and improved	Criterion 3: clinical composite (NPC and PFV both normal)	Criterion 4: composite of clinical and symptoms (NPC, PFV, CISS all normal)
Near point of convergence	Normal	<6 cm	<6 cm and improved ≥4 cm	NPC <6 cm and PFV pass Sheard's criterion and BO break finding >15Δ	NPC <6 cm and PFV pass Sheard's criterion and BO break finding >15Δ and CISS <21
Positive fusional vergence	Improved	Improved ≥4 cm
	Normal	Pass Sheard's criterion and BO break finding >15Δ	Pass Sheard's criterion and BO break finding >15Δ and increase of ≥10Δ
CISS score	Improved	Increase of ≥10Δ
	Normal	CISS <21	CISS <21 decrease of ≥10 points	NA
	Improved	Decrease of ≥10 points

BO break = base-out break; CISS = Convergence Insufficiency Symptom Survey; NA = not applicable; NPC = near point of convergence; PFV = positive fusional vergence; Δ = prism diopter.

For the first criterion, we analyzed each of the three outcome measures individually (i.e., after therapy, we determined whether the near point of convergence was normal or improved, and whether it was the same for positive fusional vergence and the CISS symptom score). For criterion 2, we determined whether each outcome measure was both normal and improved by a given magnitude. Because the measure must reach a normal level and improve a certain amount, it is a more stringent criterion than criterion 1. The third criterion analyzed both clinical measures as a composite unit. To be considered successful, both the near point of convergence and positive fusional vergence had to reach normal levels. Criterion 4 is similar to criterion 3, except that the CISS symptom score also had to be normal for the outcome to be considered successful.

RESULTS

Enrollment and Baseline Characteristics

Between August 2015 and April 2018, 220 eligibility examinations were performed for participants within the local area who self-reported they had visual symptoms, with 53 participants (24%) considered eligible. Three participants chose not to enroll because of the amount of time commitment to the study, and 50 participants enrolled and completed both the baseline and outcome sessions of the study. The mean ages of the participants who completed the study were 21.1 ± 3.6 years (44% female) and 20.6 ± 3.1 years (56% female) for participants in the vergence/accommodative therapy and placebo therapy cohorts, respectively. All baseline demographic and clinical characteristics were published previously and were similar in both treatment groups. Table 2 displays the baseline, outcome, and change in parameters for the three main outcome measures.

TABLE 2 - Change in outcomes measures by treatment group

Outcome measure	Vergence/accommodative therapy, mean (95% CI)	Placebo therapy, mean (95% CI)
Near point of convergence break (cm)
Baseline	10.5 (9.1 to 12.0)	10.3 (9.0 to 11.6)
Outcome	4.5 (3.9 to 5.2)	7.2 (6.1 to 8.3)
Change	−6.0 (−7.5 to −4.5)	−3.1 (−4.1 to −2.2)
Positive fusional vergence blur or break (Δ) at near
Baseline	11.6 (9.6 to 12.3)	10.5 (9.0 to 11.0)
Outcome	28.9 (24.1 to 33.0)	17.9 (15.0 to 20.8)
Change	17.3 (15.6 to 22.2)	7.4 (4.1 to 10.8)
CISS score
Baseline	34.0 (30.4 to 37.5)	35.1 (33.0 to 38.0)
Outcome	21.6 (10.8 to 17.0)	25.0 (21.9 to 28.2)
Change	−12.4 (−16.6 to −8.0)	−10.1 (−15.0 to −5.9)

CI = confidence interval; CISS = Convergence Insufficiency Symptom Survey; Δ = prism diopter.

Visit Completion and Home Therapy Adherence

The primary outcome visit was completed by 25 participants (100%) in the vergence/accommodative group and by 100% of the 25 participants in the placebo group. One hundred percent of the 12 office-based therapy appointments were completed for all 50 participants. Several office visits were rescheduled because of conflicts, which primarily included common sickness or work responsibilities. The goal was to have two 1-hour office visits per week. Forty-six participants (92%) finished the therapy within 8 weeks, and 50 participants (100%) completed within 12 weeks.

A total of 18 home sessions were required for each therapy. On average, 4.3 sessions with a standard deviation of 4.4 sessions were completed for the vergence/accommodative therapy group. On average, 5.4 sessions with a standard deviation of 4.7 sessions were completed for the placebo group. The patient compliance rates for the home sessions corresponding to the vergence/accommodative therapy and placebo group cohorts were 24 and 30%, respectively. No adverse events were reported.

Masking of Participants and Examiner

There were no occurrences of unmasking of the examiner at the outcome visit for either therapy group. The masked examiner did not have access to the original baseline measurement during the outcome examination. When participants were asked at the completion of treatment which therapy they thought they had received, 25 (100%) of 25 assigned to vergence/accommodative therapy thought they were in real therapy, with 21 (84%) of 25 stating they were either very sure or pretty sure of their response. For those assigned to the placebo therapy, 19 (76%) of 25 thought they were in real therapy, where 40% stated they were either very sure or pretty sure of their response.

Main Clinical Signs and Symptoms Outcome Measures

The means and 95% confidence intervals at baseline and outcome and the treatment group comparisons for the change in near point of convergence, positive fusional vergence, and CISS scores for participants who completed their outcome visit are described hereinafter and shown in Table 2.

Clinical Outcome Measure of Near Point of Convergence

There was a statistically significant mean improvement (decrease) in near point of convergence in the vergence/accommodative therapy group (−6.0 cm) compared with the placebo therapy group (−3.1 cm; difference of −2.9 cm; 95% confidence interval, −4.7 to −1.0 cm; P < .01). Using a χ² test, a significantly greater proportion of participants in the vergence/accommodative therapy group than in the placebo group were observed to meet both normal or improved success criterion 1 for near point of convergence (normal or improved by ≥4 cm; 88 vs. 52%; P < .005, χ² = 7.7; Table 3). Significantly more participants in the vergence/accommodative therapy group compared with the placebo therapy group also showed success using criterion 2, which is more stringent, requiring both normal and improved by ≥4 cm (56 vs. 24%; P = .02, χ² = 5.3).

TABLE 3 - Percentage of participants in each treatment group classified as normal or improved for each outcome measure

Outcome	Therapy group	n	Condition, % (n)
			Receded NPC but improved ≥4 cm	Normal NPC but improved <4 cm	Normal NPC and improved ≥4 cm	Normal NPC and/or improved ≥4 cm
Near point of convergence (cm)	OBVAT	25	16 (4)	24 (6)	56 (14)	88 (22)
	OBPT	25	56 (14)	20 (5)	24 (6)	52 (13)
			Insufficient PFV but improved ≥10∆	Normal PFV but improved <10∆	Normal PFV and improved ≥10∆	Normal PFV and/or improved ≥10∆
Positive fusional vergence blur or break (∆)	OBVAT	25	0 (0)	12 (3)	76 (19)	88 (22)
	OBPT	25	0 (0)	28 (7)	36 (9)	64 (16)
			CISS still ≥21 but improved ≥10 points	CISS <21 but improved <10 points	CISS <21 and improved ≥10 points	CISS <21 and/or improved ≥10 points
CISS	OBVAT	25	4 (1)	12 (3)	48 (12)	64 (16)
	OBPT	25	24 (6)	0 (0)	28 (7)	52 (13)

CISS = Convergence Insufficiency Symptom Survey; NPC = near point of convergence; OBPT = office-based placebo therapy; OBVAT = office-based vergence and accommodative therapy; PFV = positive fusional vergence; ∆ = prism diopter.

Clinical Outcome Measure of Positive Fusional Vergence at Near

The mean improvement in positive fusional vergence was 17.3 versus 7.4Δ for participants assigned to the vergence/accommodative therapy group and the placebo therapy group, respectively, with a mean treatment group difference of 9.9∆ (95% confidence interval, 4.9 to 16.0∆; P < .001; Table 3).

Clinical Outcome Measure of Amplitude of Accommodation

Monocular amplitudes of accommodation at baseline for the convergence insufficiency cohort who was randomized to vergence/accommodative therapy were 8.33 ± 2.54 D for the right eye and 8.36 ± 2.39 D for the left eye. For the convergence insufficiency cohort who was randomized to placebo therapy, their baseline amplitudes of accommodation were 8.60 ± 1.84 D for the right eye and 8.35 ± 1.96 D for the left eye. For the convergence insufficiency cohort after vergence/accommodative therapy, the amplitudes of accommodation increased to 10.90 ± 2.57 D for the right eye and 10.8 ± 2.1 D for the left eye, and for the cohort after placebo therapy, the amplitudes of accommodation increased to 9.90 ± 1.78 D for the right eye and 9.71 ± 1.79 D for the left eye. There was no significant difference between the baseline data for the convergence insufficiency participants who were being randomized into placebo compared with the vergence/accommodative therapy for the right-eye amplitude of accommodation (95% confidence interval, −1.5 to 1; P = .70) or the left-eye amplitude of accommodation (95% confidence interval, −1.2 to 1.3; P = .99). The changes in amplitude of accommodation were 2.53 ± 3.83 and 2.32 ± 3.17 D for the right and left eyes, respectively, for the vergence/accommodative therapy cohort and 1.31 ± 2.39 and 1.37 ± 2.40 D for the right and left eyes, respectively, for the placebo therapy group. Although more improvement was observed in the vergence/accommodative therapy cohort, significant changes in amplitude of accommodative were not observed between the groups (P > .20).

Clinical Outcome of Vergence Facility

Vergence facility at baseline for the convergence insufficiency participants who were randomized into vergence/accommodative therapy was 9.2 ± 7.5 cycles/min. This value was not significantly different compared with the convergence insufficiency participants who were randomized into placebo therapy and had an average of 8.1 ± 6.9 cycles/min (P = .60). After therapy, the vergence/accommodative therapy group improved to 18.4 ± 5.0 cycles/min, and the placebo therapy group improved to 15.5 ± 8.0 cycles/min. The improvement of 9.2 ± 7.1 cycles/min from the vergence/accommodative therapy group was not significantly greater than the improvement of 7.5 ± 7.7 cycles/min from the placebo therapy group (P = .40).

A statistically significant percentage of participants assigned to vergence/accommodative therapy (88%) as compared with placebo therapy (64%) met success criterion 1 (normal or improved ≥10Δ) for change in positive fusional vergence (P < .05, χ² = 4; Table 3). Likewise, there were a statistically significant proportion of vergence/accommodative participants (76%) who achieved the stricter success criterion 2 (normal and improved ≥10Δ) compared with the proportion of placebo therapy participants (36%; P < .004, χ² = 8.1; Table 3).

Symptom Outcome Measure: CISS Score

There was not a statistically significant mean treatment group difference for the CISS (2.3 points; 95% confidence interval, −8.3 to +4.6 points; P = .60; Table 3). The within-group mean improvements (decrease) in CISS scores were statistically significant and clinically meaningful for both the vergence/accommodative (12.4 points) and the placebo therapy (10.1 points) groups (P < .001 for the improvements in both groups).

The proportion of participants meeting CISS success criterion 1 for normal (<21) or improved (≥10-point decrease) symptoms was not statistically different (64 vs. 52%) in the vergence/accommodative and the placebo therapy groups, respectively (P = .40, χ² = 0.7; Table 3). Similarly, there was no statistically significant difference using the stricter success criterion 2 (normal and improved ≥10 points); 48 and 28% of participants in the vergence/accommodative therapy and the placebo therapy groups, respectively, met this criterion (P = .15, χ² = 2; Table 3).

Composite Outcome Measures

The proportion of participants who met success criterion 3 (composite convergence outcome criterion of both a normal near point of convergence and a normal positive fusional vergence) was statistically greater in the vergence/accommodative therapy group (72%) than in the placebo therapy group (32%; P < .005, χ² = 8).

A significantly greater proportion of participants in the vergence/accommodative therapy group (48%) than in the placebo therapy group (8%) were classified as successful based on success criterion 4 (composite sign and symptom outcome classification^2,5; P < .002, χ² = 9.9). Similarly, combining participants who were successful or improved based on success criterion 4 revealed that significantly more participants from the vergence/accommodative therapy group (60%) than in the placebo therapy group (16%) were successful or improved (P < .001, χ² = 10.3).

DISCUSSION

After twelve 1-hour treatment sessions, office-based vergence/accommodative therapy was found to be significantly more effective than office-based placebo therapy for improving the clinical measures of near point of convergence and positive fusional vergence in young adults. However, the improvements found in symptoms, as measured by the CISS, were not significantly different between the two treatment groups. Significant improvements in vergence facility and amplitude of accommodation were also not observed.

The differences in the mean improvements in both the near point of convergence and positive fusional vergence were both statistically significant and clinically meaningful when comparing outcome with baseline measures for the office-based vergence/accommodative therapy. For both outcome measures, the between-group (office-based vergence/accommodative therapy vs. placebo therapy) differences were greater than a standard deviation for the measurement. In addition, the composite outcome measures demonstrate a very significant 40% difference in the percentage of participants who achieved normal function in both clinical measures and would therefore no longer be considered to have convergence insufficiency (72% vergence/accommodative therapy vs. 32% placebo therapy). When we included normalization of both clinical signs and symptoms, there was again a 40% difference in success between the two groups (48% vergence/accommodative therapy group vs. 8% placebo group).

We were able to retrieve six other randomized clinical trials that investigated the effectiveness of office-based vision therapy for the treatment of symptomatic convergence insufficiency in adults.^{2,9,10,21–23} Although there is reasonably good homogeneity in these studies in regard to the diagnostic and eligibility criteria (except for one study that enrolled older adults with a mean age of 63.9 years²²), this is not true for the type and amount of therapy provided, the nature of the control group, and the outcome measures. Only two other studies used a placebo control group,^2,23 but one of these studies had a sample size of only seven subjects.²³ In addition, all but one of these studies² have significant design limitations that suggest a high likelihood of bias, such as unmasked examiners^9,10,22,23 and inadequate information on allocation concealment,^9,10,22,23 and other studies had small sample sizes.^9,23 These factors make it difficult to compare our results with previous studies. The only study that had a low risk of bias and used similar diagnostic, eligibility, and outcome criteria was a study performed by the Convergence Insufficiency Treatment Trial Investigator group.² In this Convergence Insufficiency Treatment Trial Investigator study, 46 young adult participants (mean age, 24.3 years) were enrolled and randomized to office-based vergence/accommodative therapy, office-based placebo therapy, or home-based pencil push-ups.⁸ The results were very similar to the present study, with statistically significant differences between the vergence/accommodative group and the placebo group for the near point of convergence and positive fusional vergence but not for the CISS.⁸ This Convergence Insufficiency Treatment Trial Investigator study did not use any of the composite criterion measures used in the Convergence Insufficiency Neuro-mechanism in Adult Population Study, so we are unable to compare these outcomes.⁸ However, in the Convergence Insufficiency Treatment Trial Investigator study, the authors established a criterion described as “cured,” which required a CISS of <21 and a normal near point of convergence and positive fusional vergence. Using the cured criteria, 25% (3/12) of the subjects in the vergence/accommodative group achieved this level of success compared with 0% (0/13) in the placebo group.⁸

This Convergence Insufficiency Neuro-mechanism in Adult Population Study of young adults with convergence insufficiency could also be compared with pediatric randomized clinical trials investigating office-based vergence/accommodative therapy. Table 4 presents a compilation of the results from randomized clinical trials, with both pediatric and young adult participants, which provided adequate information on randomization and masking and had a placebo control group. Although it is reasonable to speculate that the effectiveness of treatment of symptomatic convergence insufficiency might differ for children and presbyopic adults,²⁴ there is little reason to suspect that the effectiveness for improving clinical measures would differ significantly for children compared with young adults younger than 25 years. The mild decline in the amplitude of accommodation from age 11 years (expected average of 14 D) to age 25 years (expected average of 10 D) might have some impact, but given the low AC/A ratio present in convergence insufficiency, this decline would not be expected to have a significant negative impact on treatment outcomes. The data in Table 4 support the statement that the results for the clinical measures that define convergence insufficiency are comparable for children and young adults. The mean near point of convergence at outcome varies by only 1.3 cm across the studies, and positive fusional vergence (measured at near) varies by only 4.6Δ. Neither is considered clinically significant.

TABLE 4 - CINAPS outcome results compared with previous randomized clinical trials

Study	Mean age (y)	Near point of convergence (cm)		Positive fusional vergence (Δ)		CISS score
		Vergence/accommodative therapy	Placebo therapy	Vergence/accommodative therapy	Placebo therapy	Vergence/accommodative therapy	Placebo therapy
Change from baseline to outcome examination*
CINAPS adults (n = 50)	20.9	6.0	3.1	17.3	7.4	12.4	10.1
CITT adult pilot (n = 46)8	24.3	7.5	4.9	18.4	6.0	15.8	12.3
CITT children pilot (n = 47)2	11.5	9.2	6.2	19.3	7.7	22.6	6.5
CITT children (n = 221)4	11.8	10.4	3.9	19.7	6.9	14.8	7.8
CITT-ART children (n = 310)5	10.8	10.0	6.6	22.2	8.5	11.1	10.3
Mean at outcome examination*
CINAPS adults (n = 50)	20.9	4.5	7.2	28.9	17.9	21.6	25.0
CITT adult pilot (n = 46)8	24.3	5.3	9.6	29.7	17.5	20.7	26.5
CITT children pilot (n = 47)2	11.5	4.5	9.3	31.8	19.8	9.5	24.2
CITT children (n = 221)4	11.8	4.0	10.3	30.5	17.8	15.0	21.9
CITT-ART children (n = 310)5	10.8	4.0	8.3	33.5	19.6	17.0	20.1

*After 12 hours of therapy for all studies except CITT-ART (16 hours of therapy). ART = Attention and Reading Trial; CINAPS = Convergence Insufficiency Neuro-mechanism in Adult Population Study; CISS = Convergence Insufficiency Symptom Survey; CITT = Convergence Insufficiency Treatment Trial; Δ = prism diopter.

As in previous randomized clinical trials studying the effectiveness of vision therapy for convergence insufficiency, within-group improvements were found in both the near point of convergence and positive fusional vergence even in the placebo group, although these changes were significantly less than those observed in the office-based vergence/accommodative therapy group.^1,2,5,25 Because a no-treatment group was not included, it is not known whether these placebo group improvements were due to a placebo effect, regression to the mean, or natural history of the disease. The observed improvements were likely to be due to a combination of these factors.

An interesting finding of the Convergence Insufficiency Neuro-mechanism in Adult Population Study, a recent randomized clinical trial with pediatric participants,⁵ and the previous Convergence Insufficiency Treatment Trial Investigator trial with young adults² is the lack of a significant difference between therapeutic group change in symptoms. In all trial studies, both the vergence/accommodative therapy and placebo groups achieved statistically and clinically significant improvement in the CISS symptom score. In the previous Convergence Insufficiency Treatment Trial Investigator adult study, the authors argued that perhaps young adults in college or in the workforce spend more time reading or using computers or experience more nonvisually related symptoms that might mimic the visual symptoms tested on the CISS and thus remain symptomatic even after treatment. In the Convergence Insufficiency Treatment Trial—Attention and Reading Trial results, the authors speculated that the increased use of electronic devices may have impacted the validity of the CISS since its development approximately 20 years ago and that comorbid ocular (e.g., dry eye and allergies) or even nonocular conditions may result in positive responses on the CISS,^26,27 which could account for the lack of a relationship between the severity of clinical signs and the intensity of symptoms. We concur with the suggestion from the Convergence Insufficiency Treatment Trial—Attention and Reading Trial group that “it may be necessary to revise the CISS for use as an outcome measure in future studies of convergence insufficiency.”⁵

In this study, home-based therapy was all computer based, and this allowed us to objectively measure participant adherence by accessing computer activity log files. Participant adherence to the home-based therapy was low in this study, with only 24 and 30% of participants completing the prescribed therapy sessions in the vergence/accommodative therapy and placebo therapy groups, respectively. These numbers are considerably lower than previous studies.^1,2,5,25 However, it is difficult to directly compare adherence to home-based therapy with previous Convergence Insufficiency Treatment Trial Investigator studies because of differences in how adherence was measured, age of the participants (children vs. adults), and differences in the therapy procedures prescribed. In this study, adherence was calculated as the percentages of therapy sessions completed, whereas in previous studies, adherence was based on the therapist subjective determination of therapy adherence based on interview and homework sheets. The large-scale Convergence Insufficiency Treatment Trial Investigator study² did have a comparable home-based computer therapy component, and adherence (adhered to the home-based therapy protocol at least 75% of the time) was 67.3%, and in the Convergence Insufficiency Treatment Study, which also used home-based computer program, adherence was 49%.⁴ There are at least two reasons for these lower rates of adherence. First, in the Convergence Insufficiency Neuro-mechanism in Adult Population Study, adherence was measured objectively versus the subjective measures used in the Convergence Insufficiency Treatment Trial Investigator study, and we suggest that the objective measure is likely to be less biased. Second, our population consisted entirely of university students with their own set of educational and life challenges that may have impacted on their ability to find the time to adhere to the home-based therapy regimen. The important message from this study, which supports the results of previous studies, is that patients are unlikely to comply with home-based therapy, and this could be one reason why success rates for home-based vision therapy are considerably lower than success rates for office-based vision therapy.^1–5

A series of masked clinical examinations during the therapy and after outcome measurements would have been valuable and is a study limitation.

CONCLUSIONS

Office-based vergence/accommodative therapy was significantly more effective in improving near point of convergence and positive fusional vergence range compared with office-based placebo therapy in a young adult population with symptomatic convergence insufficiency within a double-masked longitudinal randomized clinical trial.