Strabismus

PURPOSE: To determine the success rate and complications associated with nasal transposition of the split lateral rectus muscle (NTSLR) for treating bilateral 3rd-nerve palsy. DESIGN: Retrospective, interventional case series. METHODS: An international, multicenter registry was used for the study. The study population was all patients with bilateral 3rd-nerve palsy treated with NTSLR. Sensorimotor evaluations were conducted before and 6 months after unilateral or bilateral NTSLR. Outcome measures were postoperative horizontal alignment ≤15 prism diopters (PD), intraoperative technical difficulties, and vision-threatening complications. The association of patient demographics and surgical technique with each outcome was analyzed using multivariable logistic regression. RESULTS: A total of 34 patients were included, with a median age of 46 years (interquartile range [IQR] = 25-54 years) at surgery. The most common etiologies were ischemic (29%), neoplastic (15%), and congenital (12%). NTSLR performed unilaterally with alternative surgery on the opposite eye (65%) resulted in a median postoperative exotropia of 18 PD (IQR = 7-35 PD), and when performed bilaterally (35%) resulted in postoperative exotropia of 14 PD (IQR = 5-35 PD). Success was achieved in 50% of cases, intraoperative technical difficulties were reported in 18%, and vision-threatening complications occurred in 21%. Attachment of the lateral rectus muscle ≥10 mm posterior to the medial rectus insertion was associated with increased vision-threatening complications (odds ratio = 9.0; 95% CI = 1.3-99). CONCLUSIONS: NTSLR can address the large-angle exotropia associated with bilateral 3rd-nerve palsy. Surgeons should be aware that posterior placement of the lateral rectus muscle may increase the risk of vision-threatening complications, particularly serous choroidal effusion.

PURPOSE: To report the indications, operative strategies, and surgical outcomes of patients who undergo vertical and horizontal rectus muscle surgery for incomitant strabismus despite being orthophoric in primary gaze. DESIGN: Retrospective, interventional case series. METHODS: The setting for this study was an academic practice at Boston Children's Hospital. The patient population comprised 8 orthophoric patients who underwent strabismus surgery to treat vertical/horizontal incomitance. Observation procedures included review of surgical strategies, strabismus measurements in diagnostic gaze positions, and development of postoperative diplopia. The main outcome measures were preserved single vision in primary gaze, comitance, reoperation rate, and patient/surgeon satisfaction. RESULTS: Surgical strategies included the following: (1) simultaneous recession of ipsilateral antagonist rectus muscles; (2) recession or resection of 1 rectus muscle with balancing surgery on the fellow eye; (3) restricting the range of 1 muscle (combined resection and recession or posterior fixation suture); and (4) creating an acceptable deviation in primary gaze. Mean follow-up was 5.4 months (median, 2 months; range, 2-25 months). No patient had new-onset primary gaze diplopia. The median incomitance improved by 9.5 prism diopters. No patient required additional surgery. Patient satisfaction and surgeon assessment of outcomes were high. CONCLUSIONS: Although the risk of operating on orthophoric patients with incomitant strabismus may discourage surgeons from offering treatment, the use of specific strategies to address incomitance can preserve alignment in primary gaze while improving patient satisfaction. These strategies may also benefit patients with incomitant strabismus that is symptomatic in primary gaze.

PURPOSE: To study methods and adverse events of postoperative, sedated suture adjustment after strabismus surgery in the post-anesthesia care unit (PACU). METHODS: We reviewed the postoperative experience of all children ≤18 years of age undergoing adjustable suture strabismus surgery at Boston Children's Hospital over a 3-year period. Time in the hospital, adverse events, and surgical outcomes were reviewed to evaluate safety and healthcare resource utilization. RESULTS: Of 356 patients, 113 required suture adjustment in the PACU, including 24 adjusted while awake and 89 adjusted under sedation. For sedation, sequential boluses of propofol were administered until adjustment was complete. Complete data from the sedated adjustment was available in 76 patients. The median initial bolus was 30 mg; the median total propofol rate was 273 mcg/kg/min. Twelve patients (16%) required only a single bolus of propofol. Of remaining 64 patients, median time from initial to final propofol dose was 7 minutes. Median anesthesiologist time in the PACU was 13 minutes. In the sedated adjustment group, there were no clinically significant adverse events, and the pain score never exceeded 6 (of a possible 10). Median duration of PACU stay was shortest in the group not requiring adjustment. CONCLUSIONS: Sedated suture adjustment allows for fine-tuning of postoperative binocular alignment in children and uncooperative adults. No adverse events were observed in our study group, but the procedure does increase the time patients spend in the hospital. This work will inform disclosure of risks and benefits of sedated adjustment while allowing for more accurate assessment of the cost and quality of adjustable sutures in children.

PURPOSE: To evaluate the surgical success and need for adjustment due to overcorrection in patients who undergo inferior oblique myectomy (IOM) combined with lateral rectus recession (LRc) for intermittent exotropia in the setting of inferior oblique overaction. METHODS: A retrospective chart review was conducted of patients with intermittent exotropia who underwent LRc using adjustable sutures alone versus LRc combined with IOM between January 2010 and July 2018 at our institution. Binocular alignment was recorded before and within one week of surgery. Evaluation measures noted were surgical success (defined as distance alignment of ⩽10 prism diopters) and need for postoperative adjustment due to overcorrection. RESULTS: Of 48 patients, 24 underwent LRc alone and 24 underwent LRc combined with IOM; all 48 patients had adjustable sutures. Surgical success was significantly higher in the LRc alone group (91.6%) compared with the LRc with IOM group (62.5%) (p = 0.036). The need for postoperative adjustment due to overcorrection was also significantly higher in the LRc with IOM group (20.8%) compared with the LRc alone group (0%) (p = 0.049). CONCLUSIONS: In this study, more patients needed adjustment for overcorrection after undergoing LRc combined with IOM versus LRc alone. Since the tertiary action of the inferior oblique is abduction it is possible that, in patients with inferior oblique overaction, surgically weakening the inferior oblique causes more esodeviation and overcorrection. Thus, surgical correction of exotropia and inferior oblique overaction using LRc combined with IOM may lead to overcorrection and increased need for postoperative adjustment.

BACKGROUND: The Delphi process has been widely used to delineate guidelines for the treatment of disorders for which there is little or no evidence in the published literature. The purpose of this study was to use the Delphi process to identify areas of consensus and disagreement on the definition of success after surgery for each type of strabismus. METHODS: Two rounds of electronic questionnaires were sent to 28 members of the Strabismus Success Definition Delphi Study Group. For the first round, responses to 70 questions were captured as agree (= 1) and disagree (= 2). For round 2, a total of 89 questions were captured on a Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Consensus was determined a priori at 85%. RESULTS: In both the first and second rounds, inter-rater agreement of 85% consensus was reached for only 20% of questions. Intra-rater agreement per question was low, with κ values ranging from -0.11 to 0.62. Intra-rater agreement was also low among themes, ranging from poor to fair agreement: κ = 0.25 for motor, κ = 0.28 for sensory, and κ = 0.35 for follow-up. CONCLUSIONS: This study highlights consensus areas that could be considered by researchers in designing studies and identifies areas where lack of consensus indicates that further research is needed.

The purpose of this review was to identify areas of consensus and disagreement among experts for the definition of success following strabismus surgery using the Delphi process. Three rounds of electronic questionnaires were sent to a panel of 28 strabismus experts. Throughout the process, members of the panel were masked to one another's identities to minimize the possibility of influence among members. Prior to data collection, we defined consensus as an 85% agreement on the answer to each question. Questions for which there was no consensus were reworded, and the resultant new questions were used in each subsequent round of questioning. We arrived at consensus for 23 of the 36 questions (64%). Consensus was obtained for recommending unique criteria for the definition of success for certain specific strabismus conditions. In addition, it was considered important that stereopsis and the range of single binocular vision be included in the definition of success for certain types of strabismus.

BACKGROUND/AIMS: To determine success rate and complications associated with nasal transposition of the split lateral rectus muscle (NTSLR) for treating strabismus from 3rd-nerve palsy. METHODS: An international, multicentre, registry of patients with unilateral 3rd-nerve palsy treated with NTSLR was created. Patients with concurrent surgery on the contralateral eye were excluded. Primary outcome was horizontal alignment within 15 prism dioptres (PD) of orthotropia. Incidence of technical difficulties and vision-threatening complications by 6 months post-procedure were reported. RESULTS: Ninety-eight patients met inclusion criteria. Median age was 33.5 years (IQR 10.75-46). Aetiologies included congenital (31%), neoplastic (16%) and traumatic (15%). Twenty-five per cent of patients had prior ipsilateral strabismus surgery. Median exotropia decreased from 70PD preoperatively (IQR 50-90) to 1PD postoperatively (IQR 0-15.5), with a success rate of 69%. Performing concurrent superior oblique muscle tenotomy (SOT) was independently associated with success (p=0.001). Technical challenges occurred in 30% of cases, independently associated with a history of ipsilateral strabismus surgery (p=0.01). Eleven per cent of patients had vision-threatening complications, independently associated with more posterior placement of the split lateral rectus (LR) muscle (p<0.001), and most commonly transient serous choroidal effusion. Surgical placement of the split LR muscle within 4.25 mm of the medial rectus (MR) muscle insertion reduced this risk. CONCLUSION: NTSLR significantly improved primary position alignment altered by 3rd-nerve palsy. Concurrent SOT and placement of the split LR muscle ≤4.25 mm posterior to the MR muscle insertion optimised outcomes. NTSLR proved technically challenging when prior ipsilateral strabismus surgery had been performed.

PURPOSE: To determine the incidence of and to identify characteristics predicting significant superior oblique palsy (SOP) after adjustable superior oblique suture spacer surgery for treatment of Brown syndrome. METHODS: The medical records of patients treated for unilateral Brown syndrome with adjustable suture spacers (2005-2016) were reviewed to identify possible association of age at surgery, spacer length, surgeon performing procedure, severity of Brown syndrome, preoperative hypotropia in primary position and affected side gaze, and reduction in Brown restriction on postoperative superior oblique function. "Good" postoperative superior oblique function was defined as absence of hypertropia and diplopia in primary position and no more than intermittent diplopia in downgaze comfortably fused with ≤4Δ base-down or head tilt of <10°. Presence of postoperative hypertropia in primary position with increase in downgaze met criteria for significant SOP. Postoperative Brown restriction of ≤ -2 indicated resolution of Brown syndrome. RESULTS: Median age at surgery was 59 months, interquartile range (IQR) was 32-82 months, and median spacer length was 6 mm (range, 2-7 mm) for 19 included patients. Preoperative median hypotropia was 9Δ (IQR, 0Δ-12Δ) in primary position and 18Δ (IQR, 5Δ-22Δ) in affected side gaze. Of 19 patients, 16 (84%) achieved sufficient resolution of Brown syndrome, but 6 (32%) developed significant SOP. Modest preoperative hypotropia in affected side gaze was the only predictor of significant SOP (likelihood ratio test = 7.11; P = 0.008). Logistic regression modeling enabled estimation of risk of significant SOP based on preoperative side gaze hypotropia. CONCLUSIONS: Suture spacer surgery can result in significant SOP. Risk may be predicted by magnitude of preoperative side gaze hypotropia.

Diplopia is a disappointing and, at times, unanticipated consequence of what might otherwise be considered anatomically successful strabismus surgery. In this study, we review the existing literature regarding diplopia after strabismus surgery in the context of the senior author's experience. We divide postoperative diplopia types into cases that occur in the setting of normal binocular vision (or "normal" suppression) vs. cases that are the consequence of rare or anomalous sensorial adaptations. We then discuss how to identify patients at greatest risk based on history and preoperative testing, and we offer strategies for managing these sometimes-challenging cases.

Orbital cellulitis is extremely uncommon following strabismus surgery. When it occurs, the infection has been reported to present from day 1 to within 1 week following surgery and has the potential for significant morbidity postoperatively. We report the case of a 6-year-old boy presenting with unilateral orbital cellulitis growing group A Streptococcus pyogenes on postoperative day 1, after uncomplicated bilateral medial rectus recessions. The patient had two contacts with streptococcal pharyngitis at the time of surgery but was completely asymptomatic himself. We hypothesize that these contacts may have led to the rapid onset of his orbital cellulitis.

This study proposes the use of the voxel-based morphometry (VBM) technique to investigate structural alterations of the cerebral cortex in patients with strabismus and amblyopia (SA). Sixteen patients with SA and sixteen healthy controls (HCs) underwent magnetic resonance imaging. Original whole brain images were analyzed using the VBM method. Pearson correlation analysis was performed to evaluate the relationship between mean gray matter volume (GMV) and clinical manifestations. Receiver operating characteristic (ROC) curve analysis was applied to classify the mean GMV values of the SA group and HCs. Compared with the HCs, GMV values in the SA group showed a significant difference in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, bilateral parahippocampal gyrus, and left anterior cingulate cortex. The mean GMV value in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, and bilateral parahippocampal gyrus were negatively correlated with the angle of strabismus. The ROC curve analysis of each cerebral region confirmed the accuracy of the area under the curve. Patients with SA have reduced GMV values in some brain regions. These findings might help to reveal the potential pathogenesis of SA and its relationship with the atrophy of specific regions of the brain.

PURPOSE: To determine whether botulinum toxin augments the effect of strabismus surgery in pediatric patients with large-angle infantile esotropia. DESIGN: Retrospective, comparative, case series. METHODS: Setting: Tertiary-care pediatric hospital. STUDY POPULATION: Patients with large-angle infantile esotropia. INTERVENTION: Treatment with botulinum toxin-augmented bilateral medial rectus muscle recessions ("augmented-surgery group") or traditional bilateral medial rectus muscle recessions ("surgery-only group"). MAIN OUTCOME MEASURE: The effect of surgery on ocular alignment at 4 months, measured in prism diopters of change per mm of surgery (PD/mm). RESULTS: There were 14 patients in the augmented-surgery group and 16 patients in the surgery-only group. The mean effect on alignment was significantly greater in the augmented-surgery group compared to the surgery-only group at 4 months (5.7 ± 1.3 vs 4.0 ± 1.4 PD/mm, P = .002) and at 1 year (5.4 ± 1.2 vs 3.7 ± 1.2 PD/mm, P = .002). There was a partial loss of treatment effect between 4 months and 1 year in both groups, which was similar in magnitude (P = .57). On linear regression, there was a trend toward a positive correlation between botulinum toxin dose and treatment effect, but this was not statistically significant (P = .09). CONCLUSIONS: Botulinum toxin augments the surgical effect of medial rectus muscle recession. Botulinum toxin-augmented surgery may be an alternative to traditional options for large-angle infantile esotropia. A surgical dosing table is proposed for this technique.

Botulinum toxin is an important treatment for many conditions in ophthalmology, including strabismus, nystagmus, blepharospasm, hemifacial spasm, spastic and congenital entropion, corneal exposure, and persistent epithelial defects. The mechanism of action of botulinum toxin for both strabismus and nystagmus is the neuromuscular blockade and transient paralysis of extraocular muscles, but when botulinum toxin is used for some forms of strabismus, a single injection can convey indefinite benefits. There are two unique mechanisms of action that account for the long-term effect on ocular alignment: (1) the disruption of a balanced system of agonist-antagonist extraocular muscles and (2) the reestablishment of central control of alignment by the binocular visual system. For other ocular conditions, botulinum toxin acts through transient paralysis of periocular muscles. Botulinum toxin is a powerful tool in ophthalmology, achieving its therapeutic effects by direct neuromuscular blockade of extraocular and periocular muscles and by unique mechanisms related to the underlying structure and function of the visual system.

This study aimed to calculate the dose-response relationship and predictors of visual acuity (VA) improvement following occlusion therapy at the IWK Health Center Eye Clinic and to add to amblyopia therapy dose-response relationship literature. A retrospective chart review was performed, considering patients who reached an occlusion therapy outcome at the IWK Eye Clinic between 2012 and 2019. The treatment outcome was defined as equal VA or stable VA for three consecutive clinical visits despite reported compliance. Subjective patching hours from parental reports, not prescribed hours, were used for statistical analyses. One hundred and thirty-four patients (66 females and 68 males) ages 2-11 years were included. Results showed a dose-response relationship of 224 hours/0.1logMAR increase in VA and total dose of 1344 hours for full-time occlusion and 504 hours for part-time occlusion was required to reach outcome VA. The fastest VA improvement occurred with younger age at treatment initiation, during the first 4 weeks of treatment, and in patients with strabismic and/or severe amblyopia. Classification of amblyopia, age, VA chart, initial distance VA (amblyopic eye), and treatment dose predicted the hour dose-response relationship. Dose-response relationship was faster in younger participants, in participants with strabismic and severe amblyopia, and during the first month of occlusion. Additionally, by creating a GLM model of dose-response relationship, relationship calculations can be performed. Therefore, an estimated timeline can be developed to allow allocation of clinical resources and to prepare patients for the treatment duration required and possibly increase treatment compliance.

Abnormalities in cranial motor nerve development cause paralytic strabismus syndromes, collectively referred to as congenital cranial dysinnervation disorders, in which patients cannot fully move their eyes. These disorders can arise through one of two mechanisms: (a) defective motor neuron specification, usually by loss of a transcription factor necessary for brainstem patterning, or (b) axon growth and guidance abnormalities of the oculomotor, trochlear, and abducens nerves. This review focuses on our current understanding of axon guidance mechanisms in the cranial motor nerves and how disease-causing mutations disrupt axon targeting. Abnormalities of axon growth and guidance are often limited to a single nerve or subdivision, even when the causative gene is ubiquitously expressed. Additionally, when one nerve is absent, its normal target muscles attract other motor neurons. Study of these disorders highlights the complexities of axon guidance and how each population of neurons uses a unique but overlapping set of axon guidance pathways.

Purpose: To determine whether rare copy number variants (CNVs) increase risk for comitant esotropia. Methods: CNVs were identified in 1614 Caucasian individuals with comitant esotropia and 3922 Caucasian controls from Illumina SNP genotyping using two Hidden Markov model (HMM) algorithms, PennCNV and QuantiSNP, which call CNVs based on logR ratio and B allele frequency. Deletions and duplications greater than 10 kb were included. Common CNVs were excluded. Association testing was performed with 1 million permutations in PLINK. Significant CNVs were confirmed with digital droplet polymerase chain reaction (ddPCR). Whole genome sequencing was performed to determine insertion location and breakpoints. Results: Esotropia patients have similar rates and proportions of CNVs compared with controls but greater total length and average size of both deletions and duplications. Three recurrent rare duplications significantly (P = 1 × 10-6) increase the risk of esotropia: chromosome 2p11.2 (hg19, 2:87428677-87965359), spanning one long noncoding RNA (lncRNA) and two microRNAs (OR 14.16; 95% confidence interval [CI] 5.4-38.1); chromosome 4p15.2 (hg19, 4:25554332-25577184), spanning one lncRNA (OR 11.1; 95% CI 4.6-25.2); chromosome 10q11.22 (hg19, 10:47049547-47703870) spanning seven protein-coding genes, one lncRNA, and four pseudogenes (OR 8.96; 95% CI 5.4-14.9). Overall, 114 cases (7%) and only 28 controls (0.7%) had one of the three rare duplications. No case nor control had more than one of these three duplications. Conclusions: Rare CNVs are a source of genetic variation that contribute to the genetic risk for comitant esotropia, which is likely polygenic. Future research into the functional consequences of these recurrent duplications may shed light on the pathophysiology of esotropia.

Addressing ocular misalignment secondary to partial and complete oculomotor nerve palsy presents a special challenge to the strabismus surgeon, particularly when treating patients with binocular diplopia. We review the reported surgical options and, through illustrative cases, provide our own perspective on managing this disorder.