Effects of vision therapy on near exodeviation in children with convergence insufficiency treated during the convergence insufficiency treatment trials.

PURPOSE: To report the change in the magnitude of near exodeviation in children with symptomatic convergence insufficiency successfully treated with office-based vergence/accommodative therapy in the Convergence Insufficiency Treatment Trial-Attention and Reading Trial. METHODS: A total of 131 children 9-14 years of age with symptomatic convergence insufficiency classified as successfully treated with office-based vergence/accommodative therapy at the 16-week outcome visit were included. Masked examiners measured the near ocular deviation by the prism and alternate cover test at baseline, primary outcome and 1-year post-treatment. The mean change in near deviation was calculated from baseline to primary outcome, from primary outcome to 1-year post-treatment and from baseline to 1-year post-treatment. RESULTS: Of the 131 participants successfully treated with vergence/accommodative therapy, 120 completed the 1-year post-treatment visit. A significant change in near exodeviation was observed at baseline to primary outcome (2.6Δ less exo, p < 0.001, moderate effect size d = 0.61) and at baseline to 1-year post-treatment (2.0Δ less exo; p < 0.001, small effect size d = 0.45). The change from primary outcome to 1-year post-treatment (0.6Δ more exo; p = 0.06, small effect size d = 0.11) was not significant. Forty per cent (48/120) of participants had a decrease in near exodeviation >3.5∆ (expected test/retest variability) between baseline and the primary outcome examination. Of the 120 participants, one (1.0%) was esophoric at the primary outcome and was subsequently exophoric at 1-year post-treatment. Four participants (3.3%) who were orthophoric or exophoric at the primary outcome were esophoric (all ≤3∆) at the 1-year post-treatment visit. CONCLUSION: On average, the near exodeviation was smaller in size immediately after the discontinuation of vergence/accommodative therapy (2.6∆, moderate effect size) and 1 year post vergence/accommodative therapy (2.0∆, small effect size) in children with convergence insufficiency who were successfully treated; 40% had a clinically meaningful decrease in exophoria. The development of near esophoria was rare.

Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years: A Randomized Clinical Trial.

Importance: The global prevalence of myopia is predicted to approach 50% by 2050, increasing the risk of visual impairment later in life. No pharmacologic therapy is approved for treating childhood myopia progression. Objective: To assess the safety and efficacy of NVK002 (Vyluma), a novel, preservative-free, 0.01% and 0.02% low-dose atropine formulation for treating myopia progression. Design, Setting, and Participants: This was a double-masked, placebo-controlled, parallel-group, randomized phase 3 clinical trial conducted from November 20, 2017, through August 22, 2022, of placebo vs low-dose atropine, 0.01% and 0.02% (2:2:3 ratio). Participants were recruited from 26 clinical sites in North America and 5 countries in Europe. Enrolled participants were 3 to 16 years of age with -0.50 diopter (D) to -6.00 D spherical equivalent refractive error (SER) and no worse than -1.50 D astigmatism. Interventions: Once-daily placebo, low-dose atropine, 0.01%, or low-dose atropine, 0.02%, eye drops for 36 months. Main Outcomes and Measures: The primary, prespecified end point was the proportion of participants' eyes responding to 0.02% atropine vs placebo therapy (<0.50 D myopia progression at 36 months [responder analysis]). Secondary efficacy end points included responder analysis for atropine, 0.01%, and mean change from baseline in SER and axial length at month 36 in a modified intention-to-treat population (mITT; participants 6-10 years of age at baseline). Safety measurements for treated participants (3-16 years of age) were reported. Results: A total of 576 participants were randomly assigned to treatment groups. Of these, 573 participants (99.5%; mean [SD] age, 8.9 [2.0] years; 315 female [54.7%]) received trial treatment (3 participants who were randomized did not receive trial drug) and were included in the safety set. The 489 participants (84.9%) who were 6 to 10 years of age at randomization composed the mITT set. At month 36, compared with placebo, low-dose atropine, 0.02%, did not significantly increase the responder proportion (odds ratio [OR], 1.77; 95% CI, 0.50-6.26; P = .37) or slow mean SER progression (least squares mean [LSM] difference, 0.10 D; 95% CI, -0.02 D to 0.22 D; P = .10) but did slow mean axial elongation (LSM difference, -0.08 mm; 95% CI, -0.13 mm to -0.02 mm; P = .005); however, at month 36, compared with placebo, low-dose atropine, 0.01%, significantly increased the responder proportion (OR, 4.54; 95% CI, 1.15-17.97; P = .03), slowed mean SER progression (LSM difference, 0.24 D; 95% CI, 0.11 D-0.37 D; P < .001), and slowed axial elongation (LSM difference, -0.13 mm; 95% CI, -0.19 mm to -0.07 mm; P < .001). There were no serious ocular adverse events and few serious nonocular events; none was judged as associated with atropine. Conclusions and Relevance: This randomized clinical trial found that 0.02% atropine did not significantly increase the proportion of participants' eyes responding to therapy but suggested efficacy for 0.01% atropine across all 3 main end points compared with placebo. The efficacy and safety observed suggest that low-dose atropine may provide a treatment option for childhood myopia progression. Trial Registration: ClinicalTrials.gov Identifier: NCT03350620.

Maximum atropine dose without clinical signs or symptoms.

PURPOSE: Atropine 1% has been used to slow the progression of myopia; however, it has not gained worldwide clinical acceptance because it results in clinically significant pupillary mydriasis and accommodative paralysis. Lower concentrations of atropine (0.5 to 0.01%) have been reported to be associated with fewer symptoms, while still controlling myopia. It is the purpose of this study to find the highest concentration of atropine that does not result in significant symptoms from pupillary dilation and accommodative paralysis. METHODS: A 3 × 3 phase I clinical trial paradigm was used in 12 subjects, to determine the maximum dosage of atropine which could be prescribed without creating symptoms or clinical signs of insufficient accommodation or excessive pupillary dilation. Accommodation was measured by pushouts and pupillary dilation by photography. Prior to this study, we established the following criteria for comfort: 5D or more of residual amplitude of accommodation, less than or equal to a 3 mm pupillary difference between the eyes, and a report of minimal symptoms of near vision blur or outside photophobia. RESULTS: Our results indicate that atropine 0.02% is the highest concentration that did not result in clinical symptoms and findings associated with higher dosages. Mean pupillary dilation was 3 mm, and mean accommodative amplitude was 8 diopters with this concentration. Further, reduction of the concentration of atropine from 0.02 to 0.01% did not seem to result in a decrease in clinical signs or symptoms associated with atropine. CONCLUSIONS: Atropine 0.02% is the highest concentration that does not produce significant clinical symptoms from accommodation paresis or pupillary dilation. This would be an appropriate starting point in evaluating a low dosage of atropine to slow myopic progression.

Current status on the development and treatment of myopia.

This is a review of the current literature describing the effect of atropine, bifocals, and/or contact lenses on slowing the progression of myopia. Cumulative data from a number of studies have demonstrated atropine instilled once a day in myopic eyes resulted in a 90% average reduction of myopia progression, as compared to untreated eyes, i.e., from 0.50 D/year to 0.05 D/year. Pirenzepine, a muscarinic pharmacological agent, has a minimal effect on pupil size and accommodation, and it has been shown to slow myopia by 44%. Bifocals and progressive lenses, which have been used for years to slow the progression of myopia, have recently been shown to produce, on average, only small, clinically insignificant treatment effects. However, their effectiveness is increased in children who are esophoric and have a large lag of accommodation, reducing myopia progression to between 0.25 and 0.40 D/year. Traditional correcting soft and gas permeable contact lenses, as well as novel spectacle lens designs, have not been shown to be effective in reducing myopic progression. Under-correction of the refractive error has been shown not only to be ineffective in slowing myopia, but has also been associated with an increased rate of myopia progression. Orthokeratology, using reverse geometry designed lenses, has been shown to be moderately effective in decreasing the progression of myopia by between 30 to 50% in a number of short-term, well-controlled studies, reducing myopia progression to between -0.25 and -0.35 D/year. Recently, there have been pilot studies using novel peripherally correcting soft contact lenses to slow the progression of myopia. Two of those lens designs have been shown to be moderately effective in slowing the progression of myopia, both of which had a 30% efficacy, reducing myopia progression to 0.35 D/year. In summary, myopia control is entering a new era with the use of contact lenses and pharmaceutical agents to effectively slow its progression with minimal side effects.