An analysis was conducted to examine the impact of commonly used non-surgical treatment modalities on intermittent exotropia. Seven published RCTs were included in this analysis. Of these, four studies reported data on overminus lens therapy, and four studies reported occlusion therapy. The pooled results showed that the non-surgical treatment demonstrated higher outcomes compared to observation, with greater reductions in exotropia control and angle of deviation at both distance and near. Similar results were found when comparing post-treatment near stereoacuity. Further analysis revealed that OML therapy showed a better apparent treatment effect than PTO therapy.
Surgery is the most common treatment modality for intermittent exotropia as it is directly effective in reducing the exotropia angle and promoting motor control, however, surgery still carries risks. The advantages of non-surgical treatments include no significant side effects and ease of perform. At the same time, there are some concerns with non-surgical treatment therapies, such as a significant psychological burden on the family12, skin irritation in patients with sensitive skin 5, and unsatisfactory treatment results. In addition, it does not result in a significant reduction in exotropia deviation. Therefore, the clinical application of non-surgical treatment is indeed limited in this way. By control, it is meant the frequency of manifest deviations and the ease of readjustment. In the last few years, there have been many reports exploring the impact of non-surgical treatments on control, with mixed results. In our meta-analysis, patients with intermittent exotropia benefited more from non-surgical treatment.
It should be noted, however, that there was significant heterogeneity between the two groups when comparing changes in exotropia control and distance deviation angle. In the random-effects model, heterogeneity remained evident. A sensitivity analysis was conducted to look for sources of heterogeneity and we found the study by Jit et al. to be the main source of heterogeneity7. The study focused on comparing overminus lenses therapy with observation for intermittent exotropia and developed a practical algorithm. Its ability to individually tailor the overminus lens requirements for treating exotropia was demonstrated by comparison with a fixed 2.50D overminus lens strategy, with over 74% of participants requiring a stronger overminus lens, and the efficacy of OML treatment in this study was greater than that found in the other included studies. These findings may be partly attributable to the greater efficacy of bespoke OML in treating IXT compared to standard fixed overminus power.
Part-time occlusion has been used as an anti-suppression treatment for the non-surgical management of intermittent exotropia with variable efficacy. Akbari et al found that patching therapy resulted in significant improvements in distance deviation control by using a 3-point system and in near deviation control by using a 6-point system, no significant improvement was observed in near control according to the 3-point scale. They also observed a significant improvement in near stereopsis13. A randomized controlled trial including 358 untreated patients aged 3-11 years with intermittent exotropia showed that after 6 months, the memory of the patching was slightly better than observed in terms of control scores in the near and this difference was also found in terms of control in the distance, however, it did not reach statistical significance. In addition, they did not observe a significant improvement in near stereopsis5. Alkahmous et al. evaluated the effect of occlusion treatment in 21 patients with intermittent exotropia aged 4-10 years. Using a 6-point scale, they found that 77.7% of occlusion treatment cases were successful in distance deviation control and 100% were successful in near deviation control. However, the occlusion treatment did not significantly reduce exodeviation angle14. On the other hand, Brian G. Mohney found that deterioration beyond 6 months was uncommon in children between 12 and 35 months of age, with or without occlusion treatment 3.
Overminus lenses have been suggested to improve the control ability of exodeviation by increasing accommodative convergence. Overall, most researchers agree about the positive therapeutic effects of overminus lens. A retrospective study by Bayramlar et al. assessing the effectiveness of overminus lens in patients with intermittent exotropia showed that according to the Newcastle Control System (NCS) and Jampolsky's assessment, 84% of these patients achieved well control scores after a mean follow-up of 18 months, and the distant angle decreased from 25 prism diopters (PD) at baseline to 18 PD after overminus lens treatment (p = 0.002)15. Another study included 24 patients aged 3-11 years with intermittent exotropia and reported that overminus lens treatment significantly reduced the distance exotropia angle and improved the control leverage 16. A retrospective study of 21 children aged 1-9 years with IXT found a 5-year improvement rate of 51% with overminus lens therapy using the NCS system 17. Kaveh Abri Aghdam reported that in a retrospective study of 163 patients with IXT, 109 patients (66.8%), based on Jampolsky's qualitative assessment method, attained good controlled IXT or orthotropia after 1 year of overminus lens treatment18.
Our meta-analysis found that both non-surgical treatments were effective in reducing near and distance control scores and in reducing the angle of exodeviaton at distance, and that overminus lenses also reduced the angle of exodeviation at near, whereas part-time occlusion did not, and neither improved stereopsis at near. Overminus lenses were superior to part-time occlusion in terms of reducing the angle of deviation and increasing the deviation control. Similar to a previous study demonstrating that overminus spectacle therapy was more effective than PTO therapy in controlling IXT, the authors emphasize that poor compliance with PTO therapy reduces its efficacy8.
Notably, myopic shift due to overcorrecting minus lenses is one of the most frequently expressed concerns of clinicians in patients with IXT. A retrospective study of 153 intermittent exotropia patients comprising 74 patients treated with overminus lenses for at least 6 months,34 patients treated with overminus lenses for 5 years and 45 patients who did not receive overminus lenses therapy found the mean myopic shift was -1.52±1.80D in the 6-month treatment group, -1.54±1.80D in the 5-year treatment group, and -1.40±2.80 D in the control group after 5 years follow up, the difference in myopic shift did not reach statistical significance19. F J Rowe identified 21 patients aged 1-9 years diagnosed with intermittent exotropia in whom they received overminus lenses therapy. Consistent with the results of previous studies, myopia shift over a median of 3 years was -0.61 ± 0.87D, reflecting the normal developmental changes of refractive error through time17. However, the sample size of the above studies was limited, and the quality was not high. More recently, two high-quality, well-designed randomized controlled studies found that overcorrection of minus lenses induced significantly higher levels of myopia than observed6,7. The results of our meta-analysis showed a WMD of -0.32 D (95% CI, -0.43 to -0.21 D) for a myopic shift in the overminus groups. Jit B. Ale Magar found that myopic individuals were associated with a greater risk of myopic shift. Special care should be taken when prescribing overminus lens treatment for IXT patients with myopic.
One randomized clinical trial was excluded from our meta-analysis because the patients in that study were treated with overcorrecting minus lenses in combination with prismatic lenses. The results of this combined treatment were better than all included studies, with mean external strabismus control scores of 1.75 ± 1.18 and 5.72 ± 1.28 (95% CI: -4.63 to -3.33) in the treatment and observation groups, and mean near stereopsis of 1.91 ± 0.26 log arcsec and 2.16 ± 0.42 log arcsec (95% CI: - 0.44 to -0.06) at last follow-up. Although this study was not included in our meta-analysis, we believe it would be valuable in helping us explore the efficacy of OML combined with other non-surgical treatment modalities in the treatment of IXT20.
In our meta-analysis, change in control was selected as the primary measure of treatment outcome. Based on previous studies, non-surgical treatment appears to be less effective in reducing the exodeviation angle, control ability is a more appropriate marker for predicting efficacy. On the other hand, if control scores, angle of exodeviation, and stereopsis at the last visit are chosen as the main comparators, results may be influenced by baseline values. For example, in Merna's study, baseline control scores were much lower in the observation group than in the non-surgical group, which directly led to lower post-treatment control score in the observation group than in the non-surgical group, however, the latter was superior to the former in terms of the amount of change in control score8. Ultimately, the change in deviation control at distance and near and the change in the angle of exodeviation at distance and near were chosen as the main indicators of comparison in our meta-analysis.
In our current study, there are several flaws and shortcomings. First, even though the sample size here is the largest and the quality of the included literature is the highest, the limited number of subjects included in this meta-analysis may have contributed to some degree of selection bias and information bias. In addition, the different overminus lens power or occlusion strategies in the included studies may have contributed to bias. Secondly, given the limited data from the included studies, our meta-analysis focused on clinical outcomes at the last follow-up rather than data collected at early, mid-term and long-term follow-ups, which may have had an impact on the current results. More detailed analyses (e.g., further subgroup analyses by follow-up period) would be required to address potential biases if sufficient clinical data were available. Finally, no additional comparisons of stereotaxic changes were performed due to the lack of relevant trial data.