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The Cochrane Database of Systematic... Sep 2021The clinical management of intermittent exotropia (X(T)) has been discussed extensively in the literature, yet there remains a lack of clarity regarding indications for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The clinical management of intermittent exotropia (X(T)) has been discussed extensively in the literature, yet there remains a lack of clarity regarding indications for intervention, the most effective form of treatment, and whether there is an optimal time in the evolution of the disease at which any given treatment should be carried out.
OBJECTIVES
The objective of this review was to analyze the effects of various surgical and non-surgical treatments in randomized controlled trials (RCTs) of participants with intermittent exotropia, and to report intervention criteria and determine whether the treatment effect varies by age and subtype of X(T).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 1), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Science Information database (LILACS); the ISRCTN registry; ClinicalTrials.gov, and the WHO ICTRP. The date of the search was 20 January 2021. We performed manual searches of the British Orthoptic Journal up to 2002, and the proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA), and American Association for Pediatric Ophthalmology and Strabismus meeting (AAPOS) up to 2001.
SELECTION CRITERIA
We included RCTs of any surgical or non-surgical treatment for intermittent exotropia.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology.
MAIN RESULTS
We included six RCTs, four of which took place in the United States, and the remaining two in Asia (Turkey, India). A total of 890 participants with basic or distance X(T) were included, most of whom were children aged 12 months to 10 years. Three of these six studies were from the 2013 version of this review. Overall, the included studies had a high risk of performance bias as masking of participants and personnel administering treatment was not possible. Two RCTs compared bilateral lateral rectus recession versus unilateral lateral rectus recession with medial rectus resection, but only one RCT (n = 197) reported on the primary outcomes of this review. Bilateral lateral rectus recession likely results in little difference in motor alignment at near (MD 1.00, 95% CI -2.69 to 4.69) and distance (MD 2.00, 95% CI -1.22 to 5.22) fixation as measured in pupillary distance using PACT (moderate-certainty evidence). Bilateral lateral rectus recession may result in little to no difference in stereoacuity at near fixation (risk ratio (RR) 0.77, 95% CI 0.35 to 1.71), adverse events (RR 7.36, 95% CI 0.39 to 140.65), or quality of life measures (low-certainty evidence). We conducted a meta-analysis of two RCTs comparing patching (n = 249) with active observation (n = 252), but were unable to conduct further meta-analyses due to the clinical and methodological heterogeneity in the remaining trials. We found evidence that patching was clinically more effective than active observation in improving motor alignment at near (mean difference (MD) -2.23, 95% confidence interval (CI) -4.02 to -0.44) and distance (MD -2.00, 95% CI -3.40 to -0.61) fixation as measured by prism and alternate cover test (PACT) at six months (high-certainty evidence). The evidence suggests that patching results in little to no difference in stereoacuity at near fixation (MD 0.00, 95% CI -0.07 to 0.07) (low-certainty evidence). Stereoacuity at distance, motor fusion test, and quality of life measures were not reported. Adverse events were also not reported, but study authors explained that they were not anticipated due to the non-surgical nature of patching. One RCT (n = 38) compared prism adaptation test with eye muscle surgery versus eye muscle surgery alone. No review outcomes were reported. One RCT (n = 60) compared lateral rectus recession and medial rectus plication versus lateral rectus recession and medial rectus resection. Lateral rectus recession and medial rectus plication may not improve motor alignment at distance (MD 0.66, 95% CI -1.06 to 2.38) (low-certainty evidence). The evidence for the effect of lateral rectus recession and medial rectus plication on motor fusion test performance is very uncertain (RR 0.92, 95% CI 0.48 to 1.74) (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Patching confers a clinical benefit in children aged 12 months to 10 years of age with basic- or distance-type X(T) compared with active observation. There is insufficient evidence to determine whether interventions such as bilateral lateral rectus recession versus unilateral lateral rectus recession with medial rectus resection; lateral rectus recession and medial rectus plication versus lateral rectus recession and medial rectus resection; and prism adaptation test prior to eye muscle surgery versus eye muscle surgery alone may confer any benefit.
Topics: Asia; Child; Exotropia; Humans; Oculomotor Muscles; Strabismus; Visual Acuity
PubMed: 34516656
DOI: 10.1002/14651858.CD003737.pub4 -
The Cochrane Database of Systematic... Dec 2020Convergence insufficiency is a common binocular vision disorder in which the eyes have a strong tendency to drift outward (exophoria) with difficulty turning the eyes... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Convergence insufficiency is a common binocular vision disorder in which the eyes have a strong tendency to drift outward (exophoria) with difficulty turning the eyes inward when reading or doing close work.
OBJECTIVES
To assess the comparative effectiveness and relative ranking of non-surgical interventions for convergence insufficiency through a systematic review and network meta-analysis (NMA).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, PubMed and three trials registers up to 20 September 2019.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) examining any form of non-surgical intervention versus placebo, no treatment, sham treatment, or other non-surgical interventions. Participants were children and adults with symptomatic convergence insufficiency.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. We performed NMAs separately for children and adults.
MAIN RESULTS
We included 12 trials (six in children and six in adults) with a total of 1289 participants. Trials evaluated seven interventions: 1) office-based vergence/accommodative therapy with home reinforcement; 2) home-based pencil/target push-ups; 3) home-based computer vergence/accommodative therapy; 4) office-based vergence/accommodative therapy alone; 5) placebo vergence/accommodative therapy or other placebo intervention; 6) prism reading glasses; and 7) placebo reading glasses. Six RCTs in the pediatric population randomized 968 participants. Of these, the Convergence Insufficiency Treatment Trial (CITT) Investigator Group completed four RCTs with 737 participants. All four CITT RCTs were rated at low risk of bias. Diagnostic criteria and outcome measures were identical or similar among these trials. The four CITT RCTs contributed data to the pediatric NMA, incorporating interventions 1, 2, 3 and 5. When treatment success was defined by a composite outcome requiring both clinical measures of convergence to be normal, and also show a pre-specified magnitude of improvement, we found high-certainty evidence that office-based vergence/accommodative therapy with home reinforcement increases the chance of a successful outcome, compared with home-based computer vergence/accommodative therapy (risk ratio (RR) 1.96, 95% confidence interval (CI) 1.32 to 2.94), home-based pencil/target push-ups (RR 2.86, 95% CI 1.82 to 4.35); and placebo (RR 3.04, 95% CI 2.32 to 3.98). However, there may be no evidence of any treatment difference between home-based computer vergence/accommodative therapy and home-based pencil/target push-ups (RR 1.44, 95% CI 0.93 to 2.24; low-certainty evidence), or between either of the two home-based therapies and placebo therapy, for the outcome of treatment success. When treatment success was defined as the composite convergence and symptom success outcome, we found moderate-certainty evidence that participants who received office-based vergence/accommodative therapy with home reinforcement were 5.12 (95% CI 2.01 to 13.07) times more likely to achieve treatment success than those who received placebo therapy. We found low-certainty evidence that participants who received office-based vergence/accommodative therapy with home reinforcement might be 4.41 (95% CI 1.26 to 15.38) times more likely to achieve treatment success than those who received home-based pencil push-ups, and 4.65 (95% CI 1.23 to 17.54) times more likely than those who received home-based computer vergence/accommodative therapy. There was no evidence of any treatment difference between home-based pencil push-ups and home-based computer vergence/accommodative therapy, or between either of the two home-based therapies and placebo therapy. One RCT evaluated the effectiveness of base-in prism reading glasses in children. When base-in prism reading glasses were compared with placebo reading glasses, investigators found no evidence of a difference in the three outcome measures of near point convergence (NPC), positive fusional vergence (PFV), or symptom scores measured by the Convergence Insufficiency Symptom Survey (CISS). Six RCTs in the adult population randomized 321 participants. We rated only one RCT at low risk of bias. Because not all studies of adults included composite success data, we could not conduct NMAs for treatment success. We thus were limited to comparing the mean difference (MD) between interventions for improving NPC, PFV, and CISS scores individually using data from three RCTs (107 participants; interventions 1, 2, 4 and 5). Compared with placebo treatment, office-based vergence accommodative therapy was relatively more effective in improving PFV (MD 16.73, 95% CI 6.96 to 26.60), but there was no evidence of a difference for NPC or the CISS score. There was no evidence of difference for any other comparisons for any outcomes. One trial evaluated base-in prism glasses prescribed for near-work activities and found that the prism glasses group had fewer symptoms compared with the placebo glasses group at three months (MD -8.9, 95% CI -11.6 to -6.3). The trial found no evidence of a difference with this intervention in NPC or PFV. No adverse effects related to study treatments were reported for any of the included studies. Excellent adherence was reported for office-based vergence/accommodative therapy (96.6% or higher) in two trials. Reported adherence with home-based therapy was less consistent, with one study reporting decreasing adherence over time (weeks 7 to 12) and lower completion rates with home-based pencil/target push-ups.
AUTHORS' CONCLUSIONS
Current research suggests that office-based vergence/accommodative therapy with home reinforcement is more effective than home-based pencil/target push-ups or home-based computer vergence/accommodative therapy for children. In adults, evidence of the effectiveness of various non-surgical interventions is less clear.
Topics: Adult; Bias; Child; Exotropia; Eyeglasses; Humans; Network Meta-Analysis; Ocular Motility Disorders; Orthoptics; Randomized Controlled Trials as Topic
PubMed: 33263359
DOI: 10.1002/14651858.CD006768.pub3 -
JAMA Ophthalmology Apr 2021This is the first large-scale randomized clinical trial evaluating the effectiveness and safety of overminus spectacle therapy for treatment of intermittent exotropia... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
This is the first large-scale randomized clinical trial evaluating the effectiveness and safety of overminus spectacle therapy for treatment of intermittent exotropia (IXT).
OBJECTIVE
To evaluate the effectiveness of overminus spectacles to improve distance IXT control.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial conducted at 56 clinical sites between January 2017 and January 2019 associated with the Pediatric Eye Disease Investigator Group enrolled 386 children aged 3 to 10 years with IXT, a mean distance control score of 2 or worse, and a refractive error between 1.00 and -6.00 diopters (D). Data analysis was performed from February to December 2020.
INTERVENTIONS
Participants were randomly assigned to overminus spectacle therapy (-2.50 D for 12 months, then -1.25 D for 3 months, followed by nonoverminus spectacles for 3 months) or to nonoverminus spectacle use.
MAIN OUTCOMES AND MEASURES
Primary and secondary outcomes were the mean distance IXT control scores of participants examined after 12 months of treatment (primary outcome) and at 18 months (3 months after treatment ended) assessed by an examiner masked to treatment group. Change in refractive error from baseline to 12 months was compared between groups. Analyses were performed using the intention-to-treat population.
RESULTS
The mean (SD) age of 196 participants randomized to overminus therapy and 190 participants randomized to nonoverminus treatment was 6.3 (2.1) years, and 226 (59%) were female. Mean distance control at 12 months was better in participants treated with overminus spectacles than with nonoverminus spectacles (1.8 vs 2.8 points; adjusted difference, -0.8; 95% CI, -1.0 to -0.5; P < .001). At 18 months, there was little or no difference in mean distance control between overminus and nonoverminus groups (2.4 vs 2.7 points; adjusted difference, -0.2; 95% CI, -0.5 to 0.04; P = .09). Myopic shift from baseline to 12 months was greater in the overminus than the nonoverminus group (-0.42 D vs -0.04 D; adjusted difference, -0.37 D; 95% CI, -0.49 to -0.26 D; P < .001), with 33 of 189 children (17%) in the overminus group vs 2 of 169 (1%) in the nonoverminus group having a shift higher than 1.00 D.
CONCLUSIONS AND RELEVANCE
Children 3 to 10 years of age had improved distance exotropia control when assessed wearing overminus spectacles after 12 months of overminus treatment; however, this treatment was associated with increased myopic shift. The beneficial effect of overminus lens therapy on distance exotropia control was not maintained after treatment was tapered off for 3 months and children were examined 3 months later.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02807350.
Topics: Child; Child, Preschool; Chronic Disease; Exotropia; Eyeglasses; Female; Humans; Male; Myopia; Refractive Errors
PubMed: 33662112
DOI: 10.1001/jamaophthalmol.2021.0082 -
PloS One 2018To compare the surgical outcomes between pre- and full-term patients with exotropia and to examine the factors associated with surgical outcomes. (Clinical Trial)
Clinical Trial
PURPOSE
To compare the surgical outcomes between pre- and full-term patients with exotropia and to examine the factors associated with surgical outcomes.
METHODS
This retrospective study included 48 pre- and 432 full-term patients with basic-type exotropia who underwent unilateral or bilateral lateral rectus muscle (ULR or BLR) recession. Preoperative characteristics and surgical outcomes were compared between the pre- and full-term infants. Additionally, factors affecting the surgical outcomes were evaluated in all patients.
RESULTS
The preoperative characteristics were significantly different between the pre- and full-term groups in terms of neurodevelopmental disabilities (p = 0.020). There were no significant differences between the pre- and full-term groups in terms of the success, overcorrection, and recurrence rates after the mean follow-up period of 34.6 ± 13.9 months (p = 0.697). The major cause of surgical failure was recurrence in both groups. Pre-term birth was not a risk factor for overcorrection and recurrence. However, regardless of the pre- or full-term birth status, the presence of neurodevelopmental disabilities significantly affected final overcorrection (p = 0.004).
CONCLUSIONS
Pre-term patients with exotropia showed similar surgical outcomes to full-term controls. The presence of neurodevelopmental disabilities was a risk factor for final overcorrection.
Topics: Adolescent; Child; Child, Preschool; Exotropia; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Premature; Male
PubMed: 30532279
DOI: 10.1371/journal.pone.0208848 -
The Cochrane Database of Systematic... May 2013The clinical management of intermittent exotropia has been discussed extensively in the literature, yet there remains a lack of clarity regarding indications for... (Review)
Review
BACKGROUND
The clinical management of intermittent exotropia has been discussed extensively in the literature, yet there remains a lack of clarity regarding indications for intervention, the most effective form of treatment and whether or not there is an optimal time in the evolution of the disease at which any treatment should be carried out.
OBJECTIVES
The objective of this review was to analyse the effects of various surgical and non-surgical treatments in randomised trials of participants with intermittent exotropia, and to report intervention criteria and determine the significance of factors such as age with respect to outcome.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library, Issue 4, 2012), MEDLINE (January 1966 to May 2012), EMBASE (January 1980 to May 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to May 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 May 2012. We are no longer searching the UK Clinical Trials Gateway (UKCTG) for this review. We manually searched the British Orthoptic Journal up to 2002, and the proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA) and American Academy of Paediatric Ophthalmology and Strabismus meeting (AAPOS) up to 2001. We contacted researchers who are active in the field for information about further published or unpublished studies.
SELECTION CRITERIA
We included randomised controlled trials of any surgical or non-surgical treatment for intermittent exotropia.
DATA COLLECTION AND ANALYSIS
Each review author independently assessed study abstracts identified from the electronic and manual searches. Author analysis was then compared and full papers for appropriate studies were obtained.
MAIN RESULTS
We found one randomised trial that was eligible for inclusion. This trial showed that unilateral surgery was more effective than bilateral surgery for correcting the basic type of intermittent exotropia.
AUTHORS' CONCLUSIONS
The available literature consists mainly of retrospective case reviews, which are difficult to reliably interpret and analyse. The one randomised trial included found unilateral surgery more effective than bilateral surgery for basic intermittent exotropia. However, across all identified studies, measures of severity and thus criteria for intervention are poorly validated, and there appear to be no reliable natural history data. There is therefore a pressing need for improved measures of severity, a better understanding of the natural history and carefully planned clinical trials of treatment to improve the evidence base for the management of this condition.
Topics: Exotropia; Humans; Randomized Controlled Trials as Topic
PubMed: 23728647
DOI: 10.1002/14651858.CD003737.pub3 -
Eye (London, England) Jul 2018Although less frequent than consecutive exotropia, consecutive esotropia is a well-known type of strabismus when it follows the surgical correction of an exotropia....
PURPOSE
Although less frequent than consecutive exotropia, consecutive esotropia is a well-known type of strabismus when it follows the surgical correction of an exotropia. Spontaneous conversion from initial constant, large-angle exotropia beyond the age of 3 months to esotropia or orthophoria, however, is not common. We describe a series of infants who presented a spontaneous evolution from a large-angle infantile exotropia to either an orthophoria or a spontaneously consecutive esotropia.
METHODS
Cases of infants examined in the pediatric neuro-ophthalmology clinic of a tertiary ophthalmology department between 2009 and 2015, and having presented an early large-angle exotropia that spontaneously converted into an esotropia or orthophoria-i.e., without any previous surgery or botulinum toxin injection-were studied.
RESULTS
Ten cases (6 M:4 F) were followed up. Median age at first exotropia assessment was 3.88 months (SD = 6.35). Median age at spontaneous conversion to esotropia or orthophoria was 7.23 months (SD = 14.73). Six patients suffered from severe neurologic or metabolic diseases, three had neonatal respiratory distress syndrome, and one was healthy.
CONCLUSION
Spontaneous conversion from initial large-angle exotropia to esotropia or orthophoria can be encountered. The cerebral maturation of visual structures probably accounts for this uncommon strabismus sequence.
Topics: Esotropia; Exotropia; Female; Humans; Hyperopia; Infant; Infant, Newborn; Male; Nervous System Diseases; Retrospective Studies
PubMed: 29497134
DOI: 10.1038/s41433-018-0060-0 -
La Tunisie MedicaleTo study the clinical particularities and the surgical management of the different forms of exotropia, and to analyze the prognostic factors influencing the surgical...
AIM
To study the clinical particularities and the surgical management of the different forms of exotropia, and to analyze the prognostic factors influencing the surgical result.
METHODS
Medical records of 132 patients who underwent exotropia surgery from 1995 to 2015, were retrospectively reviewed. Ophthalmological examination and a complete sensorimotor assessment were performed for each patient. All surgeries were performed by the same surgeon.
RESULTS
We had 57 cases of intermittent exotropia (IE), 22 cases of infantile exotropia (IfE), 43 cases of sensory exotropia (SE) and 10 cases of concecutive exotropia (CE). The average age of onset of exotropia was 6.8 years +/- 8 SD. Amblyopia was noted in 36.4% of cases of IfE. The mean deviation angle was 36.5 DP in (IE), 39.6 DP in (IfE) and 44.5 DP in (SE). A vertical syndrome was frequently found in (IfE) patients. Bilateral recession of lateral rectus was the most performed surgery type. The overall success rate after a single surgery was 72%. A multivariate logistic regression analysis showed that good prognosis factors were the absence of amblyopia, the intermittent form of the strabismus, a low preoperative deviation angle and the ocular alignment on day one postoperatively.
CONCLUSIONS
IE is the most common divergent strabismus. Surgery resulted in successful alignment in most of the cases. Early management and rigorous analysis of patients sensorimotor status are the best guarantors of long-term success.
Topics: Child; Exotropia; Follow-Up Studies; Humans; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Retrospective Studies; Treatment Outcome; Vision, Binocular
PubMed: 35244907
DOI: No ID Found -
Ophthalmology Mar 2023
Topics: Humans; Esotropia; Exotropia; Oculomotor Muscles; Ophthalmologic Surgical Procedures
PubMed: 36526451
DOI: 10.1016/j.ophtha.2022.11.002 -
BMC Ophthalmology Mar 2023We evaluate the clinical characteristics of intermittent exotropia with controllability and compare surgical outcomes between patients with and without controllability. (Review)
Review
BACKGROUND/AIMS
We evaluate the clinical characteristics of intermittent exotropia with controllability and compare surgical outcomes between patients with and without controllability.
METHODS
We reviewed the medical records of patients aged 6-18 years with intermittent exotropia who underwent surgery between September 2015 and September 2021. Controllability was defined as the patient's subjective awareness of exotropia or diplopia associated with the presence of exotropia and ability to instinctively correct the ocular exodeviation. Surgical outcomes were compared between patients with and without controllability, with a favorable surgical outcome defined as an ocular deviation between ≤ 10 PD of exotropia and ≤ 4 PD of esotropia at distance and near.
RESULTS
Among 521 patients, 130 (25%, 130/521) had controllability. The mean age of onset (7.7 years) and surgery (9.9 years) were higher in patients with controllability than in those without controllability (p < 0.001). The mean control scores of patients with controllability (distance: 1.9, near: 1.5) were lower compared with patients without controllability (distance: 3.0, near: 2.2), reflecting a better level of control. Patients with controllability had a better surgical outcome than those without controllability, as analyzed by log-rank test (p < 0.001). Larger preoperative ocular exodeviation at distance (hazard ratio [HR] = 1.083, confidence interval [CI] = 1.018-1.151, p = 0.012) and near (HR = 1.102, CI = 1.037-1.172, p = 0.002) were significantly related to recurrence in patients with controllability.
CONCLUSIONS
Patients with controllability showed better surgical outcomes, later exotropia onset, and better level of control than patients without controllability. Preoperative ocular exodeviation was a significant factor influencing favorable outcomes in patients with controllable exotropia.
Topics: Humans; Child; Exotropia; Treatment Outcome; Ophthalmologic Surgical Procedures; Oculomotor Muscles; Retrospective Studies; Follow-Up Studies; Vision, Binocular
PubMed: 36978009
DOI: 10.1186/s12886-023-02873-w -
Indian Journal of Ophthalmology May 2023To describe a clinical entity called "rectus muscle pseudo-adherence syndrome" following buckling surgery.
PURPOSE
To describe a clinical entity called "rectus muscle pseudo-adherence syndrome" following buckling surgery.
METHODS
A retrospective data review was undertaken to analyze the clinical profile of strabismus patients who had developed it following buckling surgery. Between 2017 and 2021, a total of 14 patients were identified. The demography, surgical details, and intraoperative challenges were reviewed.
RESULTS
The average age of the 14 patients was 21.71 ± 5.23 years. The mean pre-op deviation was 42.35 ± 14.35 prism diopters (PD) of exotropia, and the mean post-op deviation was 8.25 ± 4.88 PD of residual exotropia at 26.16 ± 19.53 months follow-up. Intraoperatively, in the absence of a buckle, the thinned-out rectus adhered to the underlying sclera with much denser adhesions along its margins. When there was a buckle, the rectus muscle adhered to the outer surface of the buckle again, but less densely, with marginal union into the surrounding tenons. In both scenarios, due to the absence of protective muscle coverings, the rectus muscles were naturally adsorbed onto the immediately available surface in the presence of active healing by the tenons.
CONCLUSION
While correcting ocular deviations following buckling surgery, a false sense of an absent, slipped, or thinned-out rectus muscle is very much possible. This is due to active healing of the muscle with the surrounding sclera or the buckle in a single layer of tenons. This is the rectus muscle pseudo-adherence syndrome, where the culprit is the healing process and not the muscle.
Topics: Humans; Adolescent; Young Adult; Adult; Exotropia; Retrospective Studies; Treatment Outcome; Ophthalmologic Surgical Procedures; Oculomotor Muscles; Sclera; Vision, Binocular; Follow-Up Studies
PubMed: 37203086
DOI: 10.4103/ijo.IJO_2075_22