Long-Term Outcomes of Intermittent Exotropia: A Real-World Longitudinal Cohort Study of 415 Patients
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Setting
2.2. Participants
- A confirmed clinical diagnosis of IXT.
- Documented age at presentation.
- Complete ocular alignment measurements at both distance (6 m) and near (33 cm) using the prism and alternate cover test.
- Availability of detailed preoperative, surgical, and postoperative follow-up records.
- Minimum follow-up duration of 6 months.
- Restrictive or paralytic strabismus.
- Structural ocular pathologies (e.g., cataract, retinal disease).
- Prior extraocular muscle surgery before initial evaluation.
- Significant systemic or neurological comorbidities.
- Inability to attend regular follow-up visits.
2.3. Clinical Assessments
- Best Corrected Visual Acuity testing using age-appropriate methods.
- Binocular Single Vision assessment via the Bagolini, Titmus or Randot tests.
- Ocular motility assessment and alignment measurement using the prism and alternate cover test at distance and near fixation.
- Occlusion testing: Parents were informed that at a subsequent visit the non-dominant eye would be occluded for 1 h to reveal the largest angle of deviation.
- 5.
- Dynamic retinoscopy to assess binocular accommodative function.
- 6.
- Cycloplegic refraction performed using cyclopentolate 1%.
- 7.
- Anterior and posterior segment evaluation via slit-lamp biomicroscopy and indirect ophthalmoscopy.
2.4. Treatments
2.5. Statistical Analysis
- For categorical variables, the Pearson Chi-square test, Fisher’s Exact test, or the Fisher–Freeman–Halton Exact test (in cases of small, expected cell counts) was used. Where appropriate, post hoc analyses included pairwise comparisons or adjusted residuals.
- For non-normally distributed continuous variables, comparisons between two independent groups were performed using the Mann–Whitney U test, while comparisons among more than two groups were assessed using the Kruskal–Wallis test. In cases of statistical significance, pairwise Mann–Whitney U tests were applied for post hoc evaluation.
- Within-subject comparisons of non-normally distributed variables over time were analyzed using the Friedman test, with Wilcoxon signed-rank tests for post hoc pairwise analyses.
- For repeated categorical measures, the Cochran’s Q test was used, followed by McNemar’s test for pairwise comparisons when appropriate.
2.6. Longitudinal and Survival Analyses
3. Results
3.1. Patient Demographics and Clinical Characteristics
3.2. Non-Surgical Management
3.3. Over-Minus Therapy
3.4. Longitudinal Refractive Change
3.5. Age-Related Control Analysis Among Surgically Treated Patients (n = 167)
3.6. Surgical Outcomes and Associated Factors
3.7. Surgical Procedures and Postoperative Stability
3.8. Reoperations
3.9. Changes in Binocular Sensory Function During Follow-Up
3.10. Kaplan–Meier Analysis of Surgical and Non-Surgical Outcomes
3.11. Univariate Log-Rank Analysis
3.12. Multivariate Cox Proportional Hazards Model
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
| BLR | Bilateral Lateral Rectus Recession |
| CI | Confidence Interval |
| ECS | Eye Control Scale |
| HR | Hazard Ratio |
| IQR | Interquartile Range |
| IXT | Intermittent Exotropia |
| LMM | Linear Mixed-Effects Model |
| MAR | Missing At Random |
| OML | Over-Minus Lens (Over-minus Lens) |
| PD | Prism Diopters |
| PEDIG | Pediatric Eye Disease Investigator Group |
| R&R | Recession–Resection |
| SD | Standard Deviation |
| SE | Spherical Equivalent |
| SPSS | Statistical Package For The Social Sciences (IBM SPSS Statistics) |
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| Continuous Variables | ||
|---|---|---|
| Variable | Mean ± SD | Median (IQR) |
| Age at onset (years) | 3.7 ± 2.9 | 3 (3.5) |
| Age at presentation (years) | 6.8 ± 4.9 | 6 (5.0) |
| Follow-up duration (months) | 53.2 ± 47.8 | 40 (63) |
| Categorical variables | ||
| Variable | Category | n (%) |
| Sex | Female | 243 (58.6) |
| Male | 172 (41.4) | |
| Gestational age | Term | 317 (76.4) |
| Preterm | 98 (23.6) | |
| Birth type | Vaginal | 213 (51.3) |
| Cesarean | 127 (30.6) | |
| Unknown * | 75 (18.1) | |
| Family history of strabismus/amblyopia | Positive | 74 (17.8) |
| Negative | 341 (82.2) | |
| IXT subtype | Basic | 201 (48.4) |
| Pseudo-divergence excess | 139 (33.5) | |
| Divergence excess | 59 (14.2) | |
| Convergence insufficiency | 16 (3.9) | |
| Age Group Years | XT Types—Simple | XT Types—Divergence | XT Types—Convergence | XT Types—Pseudo-D | Test Value | p |
|---|---|---|---|---|---|---|
| ≤4 | 59 (43.4%) | 25 (18.4%) | 1 (0.7%) | 51 (37.5%) | 24.735 | 0.002 |
| 4–6 years | 41 (44.6%) | 13 (14.1%) | 1 (1.1%) | 37 (40.2%) | ||
| 7–14 years | 84 (52.8%) | 18 (11.3%) | 10 (6.3%) | 47 (29.6%) | ||
| ≥15 years | 17 (60.7%) | 3 (10.7%) | 4 (14.3%) | 4 (14.3%) |
| Parameter | Group | n | Mean ± SD | Median (IQR) | Statistical Test | p-Value |
|---|---|---|---|---|---|---|
| Age at surgery (years) | No OML | 84 | 11.2 ± 7.1 | 10 (7–14) | −3.329 | 0.001 |
| OML | 83 | 7.9 ± 3.5 | 7 (5–9) | |||
| Time from first visit to surgery (years) | No OML | 84 | 1.34 ± 2.07 | 0.75 (0–2) | −2.075 | 0.038 |
| OML | 83 | 1.83 ± 2.40 | 1 (0–2) |
| Follow-Up Year | Over-Minus Group (Mean ± SD) | Surgical Group (Mean ± SD) | Mean Difference (95% CI) |
|---|---|---|---|
| Baseline | −0.10 ± 2.34 | +0.24 ± 1.44 | 0.34 (−0.21 to 0.89) |
| Year 3 | −1.05 ± 2.03 | −0.84 ± 2.41 | 0.21 (−0.48 to 0.89) |
| Year 5 | −1.61 ± 2.06 | −1.38 ± 2.63 | 0.23 (−0.61 to 1.08) |
| Year 7 | −2.10 ± 1.98 | −1.51 ± 3.02 | 0.59 (−0.42 to 1.60) |
| β (slope) | −0.25 D/year, p < 0.001 | −0.26 D/year, p < 0.001 | Interaction p = 0.541 |
| ECS Group | n | Age at Presentation (Years) | Delay from Onset to Presentation (Years) | |||||
|---|---|---|---|---|---|---|---|---|
| Mean ± SD | Median (IQR) | p | Mean ± SD | Median (IQR) | p | |||
| ECS–Near | Good (1–2) | 93 | 6.83 ± 4.59 | 6 (4–9) | 0.006 * (H = 10.285) | 3.41 ± 4.02 | 2 (1–5) | 0.038 * (H = 6.535) |
| Moderate (3) | 54 | 8.49 ± 5.82 | 7 (5–11) | 4.79 ± 5.13 | 3 (1–6) | |||
| Poor (4–5) | 19 | 11.92 ± 7.91 | 10 (7–16) | 6.02 ± 5.10 | 5 (3–9) | |||
| ECS–Distance | Good (1–2) | 18 | 6.80 ± 6.10 | 6 (4–9) | 0.155 (H = 3.731) | 3.52 ± 5.50 | 2 (1–5) | 0.014 * (H = 8.580) |
| Moderate (3) | 73 | 7.42 ± 4.75 | 7 (5–10) | 3.38 ± 4.15 | 2 (1–5) | |||
| Poor (4–5) | 74 | 8.83 ± 6.30 | 8 (6–12) | 5.13 ± 4.70 | 4 (2–8) | |||
| Parameter | Metric | Successful (n = 109) | Unsuccessful (n = 58) | p-Value |
|---|---|---|---|---|
| Overall success rate | n (%) | 109 (65.3%) | 58 (34.7%) | — |
| Age (years) * | Mean ± SD/Median (IQR) | 7.72 ± 5.42/6 (6) | 8.28 ± 6.13/6.25 (7) | 0.737 |
| Surgical age (years) * | Mean ± SD/Median (IQR) | 9.30 ± 5.65/8 (5) | 9.89 ± 6.06/9 (6.25) | 0.757 |
| IXT subtype † | n (%) | 0.771 | ||
| Basic | 49 (66.2%) | 25 (33.8%) | ||
| Divergence excess | 21 (67.7%) | 10 (32.3%) | ||
| Pseudo-divergence excess | 32 (59.3%) | 22 (40.7%) | ||
| Convergence insufficiency | 1 (100%) | 0 (0%) | ||
| Surgical type ‡ | n (%) | 0.108 | ||
| BLR | 32 (80.7%) | 11 (19.3%) | ||
| R/R | 71 (60.7%) | 46 (39.3%) | ||
| Surgical dose ‡ | n (%) | 0.461 | ||
| Standard | 43 (66.1%) | 19 (33.9%) | ||
| Augmented | 65 (63.7%) | 37 (36.3%) |
| Parameter | Category | BLR n (%) | R/R n (%) | Statistical Test | p-Value |
|---|---|---|---|---|---|
| Age group (years) * | ≤6 (n = 84) | 29 (34.5%) | 55 (65.5%) | 5.321 | 0.066 |
| 7–14 (n = 60) | 12 (20.0%) | 48 (80.0%) | |||
| ≥15 (n = 16) | 2 (12.5%) | 14 (87.5%) | |||
| Gender † | Male (n = 69) | 18 (26.1%) | 51 (73.9%) | 0.038 | 0.845 |
| Female (n = 91) | 25 (27.5%) | 66 (72.5%) | |||
| IXT subtype * | Basic (n = 74) | 14 (18.9%) | 60 (81.1%) | 11.652 | 0.005 |
| Divergence excess (n = 31) | 16 (51.6%) | 15 (48.4%) | |||
| Pseudo-divergence excess (n = 54) | 13 (24.1%) | 41 (75.9%) | |||
| Convergence insufficiency (n = 1) | 0 (0%) | 1 (100%) | |||
| Mean surgical age (years) ‡ | Mean ± SD/Median (IQR) | 6.5 ± 5.4/5 (6) | 8.3 ± 5.6/7 (6) | −2.401 | 0.016 |
| Final Fusion | Total | ||||
|---|---|---|---|---|---|
| Abnormal Fusion | Fusion | Suppression | |||
| Initial Fusion | Abnormal Fusion | 3 (6.5%) | 42 (91.3%) | 1 (2.2%) | 46 |
| Fusion | 1 (0.4%) | 229 (99.1%) | 1 (0.4%) | 231 | |
| Suppression | 1 (6.7%) | 12 (80%) | 2 (13.3%) | 15 | |
| 5 (1.7%) | 283 (96.9%) | 4(1.4%) | 292 | ||
| N | Mean | Standard Deviation | Min | Max | Median (IQR) | Test Value | p | |
|---|---|---|---|---|---|---|---|---|
| Initial Stereopsis | 255 | 1.015.69 | 1.314.20 | 40 | 3000 | 200 (2940) | −9.884 | <0.001 |
| Final Stereopsis | 255 | 244.71 | 622.48 | 40 | 3000 | 80 (40) |
| Final Stereopsis | p | ||||
|---|---|---|---|---|---|
| Absent | Present | Total | |||
| Initial Stereopsis | Absent | 26 (49.1%) | 27 (50.9%) | 53 (16.9%) | 0.000 |
| Present | 6 (2.3%) | 255 (97.7%) | 261 (83.1%) | ||
| Total | 32 (10.2%) | 282 (89.8%) | 314 (100%) | ||
| Variable | Category/Metric | n | Events | Censored (%) | Median Survival (Months, 95% CI) | χ2 (Log-Rank) | p-Value | Hazard Ratio (HR, 95% CI) | p (Cox) |
|---|---|---|---|---|---|---|---|---|---|
| Overall | — | 415 | 245 | 41.0 | 70 (60.9–79.1) | — | — | — | — |
| Sex | Male vs. Female | 172/243 | 92/153 | 46.5/37.0 | 78 (57.3–98.7)/70 (60.6–79.4) | 1.874 | 0.171 | — | — |
| Surgery | Yes vs. No | 167/248 | 58/187 | 65.3/24.6 | 147 (129.3–164.7)/42 (31.8–52.2) | 98.781 | <0.001 | 0.174 (0.120–0.252) | <0.001 |
| ECS–Near | Good (1–2) vs. Poor (3–5) | 307/105 | 192/51 | 37.5/51.4 | 69 (55.7–82.3)/79 (58.5–99.6) | 4.847 | 0.028 | 1.147 (0.806–1.633) | 0.446 |
| ECS–Distance | Good (1–2) vs. Poor (3–5) | 182/229 | 125/118 | 31.3/48.5 | 58 (41.7–74.3)/84 (70.6–97.4) | 11.324 | 0.001 | 1.421 (1.051–1.920) | 0.022 |
| Age group | <7 vs. ≥7 years | 228/187 | 138/107 | 39.5/42.8 | 76 (63.6–88.4)/63 (43.6–82.4) | 3.649 | 0.056 | 1.040 (1.010–1.070) | 0.008 |
| Over-minus therapy | Yes vs. No | 252/163 | 156/89 | 37.1/45.4 | 67 (53.0–81.0)/80 (67.5–92.6) | 2.843 | 0.092 | 1.089 (0.824–1.438) | 0.550 |
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Yilmaz Cinar, F.G.; Guvenc, U.; Akmaz, R.; Topalak, Y.; Burcu, A. Long-Term Outcomes of Intermittent Exotropia: A Real-World Longitudinal Cohort Study of 415 Patients. Medicina 2026, 62, 481. https://doi.org/10.3390/medicina62030481
Yilmaz Cinar FG, Guvenc U, Akmaz R, Topalak Y, Burcu A. Long-Term Outcomes of Intermittent Exotropia: A Real-World Longitudinal Cohort Study of 415 Patients. Medicina. 2026; 62(3):481. https://doi.org/10.3390/medicina62030481
Chicago/Turabian StyleYilmaz Cinar, Fatma Gul, Umay Guvenc, Rabia Akmaz, Yasemin Topalak, and Ayse Burcu. 2026. "Long-Term Outcomes of Intermittent Exotropia: A Real-World Longitudinal Cohort Study of 415 Patients" Medicina 62, no. 3: 481. https://doi.org/10.3390/medicina62030481
APA StyleYilmaz Cinar, F. G., Guvenc, U., Akmaz, R., Topalak, Y., & Burcu, A. (2026). Long-Term Outcomes of Intermittent Exotropia: A Real-World Longitudinal Cohort Study of 415 Patients. Medicina, 62(3), 481. https://doi.org/10.3390/medicina62030481

