Excitatory Contribution to Binocular Interactions in Human Visual Cortex Is Reduced in Strabismic Amblyopia.

Binocular summation in strabismic amblyopia is typically reported as being absent or greatly reduced in behavioral studies and is thought to be because of a preferential loss of excitatory interactions between the eyes. Here, we studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with strabismic and anisometropic amblyopia in both sexes, using source-imaged steady-state visual evoked potentials (SSVEP) over a wide range of relative contrast between the two eyes. Dichoptic parallel grating stimuli modulated at unique temporal frequencies in each eye allowed us to quantify spectral response components associated with monocular inputs (self-terms) and the response components because of interaction of the inputs of the two eyes [intermodulation (IM) terms]. Although anisometropic amblyopes revealed a similar pattern of responses to normal-vision observers, strabismic amblyopes exhibited substantially reduced IM responses across cortical regions of interest (V1, V3a, hV4, hMT+ and lateral occipital cortex), indicating reduced interocular interactions in visual cortex. A contrast gain control model that simultaneously fits self- and IM-term responses within each cortical area revealed different patterns of binocular interactions between individuals with normal and disrupted binocularity. Our model fits show that in strabismic amblyopia, the excitatory contribution to binocular interactions is significantly reduced in both V1 and extra-striate cortex, whereas suppressive contributions remain intact. Our results provide robust electrophysiological evidence supporting the view that disruption of binocular interactions in strabismus or amblyopia is because of preferential loss of excitatory interactions between the eyes.SIGNIFICANCE STATEMENT We studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with normal and amblyopic vision, using source-imaged SSVEP and frequency-domain analysis of dichoptic stimuli over a wide range of relative contrast between the two eyes. A dichoptic contrast gain control model was used to characterize these interactions in amblyopia and provided a quantitative comparison to normal vision. Our model fits revealed different patterns of binocular interactions between normal and amblyopic vision. Strabismic amblyopia significantly reduced excitatory contributions to binocular interactions, whereas suppressive contributions remained intact. Our results provide robust evidence supporting the view that the preferential loss of excitatory interactions disrupts binocular interactions in strabismic amblyopia.

Altered functional connectivity of primary visual cortex in adults with strabismus and amblyopia: a resting-state fMRI study.

Functional connectivity of the primary visual cortex was explored with resting functional magnetic resonance imaging among adults with strabismus and amblyopia and healthy controls. We used the two-sample test and receiver operating characteristic curves to investigate the differences in mean functional connectivity values between the groups with strabismus and amblyopia and healthy controls. Compared with healthy controls, functional connectivity values in the left Brodmann areas 17, including bilateral lingual/angular gyri, were reduced in groups with strabismus and amblyopia. Moreover, functional connectivity values in the right Brodmann area 17, including left cuneus, right inferior occipital gyrus, and left inferior parietal lobule, were reduced in adults with strabismus and amblyopia. Our findings indicate that functional connectivity abnormalities exist between the primary visual cortex and other regions. This may be the basis of the pathological mechanism of visual dysfunction and stereovision disorders in adults with strabismus and amblyopia.

[Functional multislice computed tomography of the orbits in diagnosis of incomitant strabismus]. / Funktsional'naya mul'tispiral'naya komp'yuternaya tomografiya orbit v algoritme diagnostiki nesodruzhestvennykh form kosoglaziya.

PURPOSE: To study the value of functional multislice computed tomography (MSCT) of the orbits in examination of patients with complex incomitant strabismus. MATERIAL AND METHODS: The study included 34 patients. In 8 (23.5%) out of 34 patients, strabismus occurred as the result of an orbital injury. In some patients, incomitant strabismus was a complication of: retrobulbar injection of drugs (4 cases (11.7%)); endoscopic sinus surgery (6 cases (17.6%)); reconstructive surgery of orbits (7 cases (20.6%)). In 9 cases (26.5%), incomitant strabismus was detected in patients with thyroid eye disease (TED), of them 5 (14.7%) had previously undergone balanced orbital decompression (BOD). All patients underwent functional MSCT of the orbits. RESULTS: Complete absence of the contractile function of the studied muscles was noted in 6 cases with loss of ocular motility in one or several directions of gaze. Contraction of the injured muscle and its fixation in the area of iatrogenic defect in the orbital wall was observed in 6 patients with severe limitation of ocular motility. limitation of the excursion of the inferior and/or medial rectus muscles due to their fixation in the fracture of the orbital wall was observed in 5 patients after orbital trauma. Signs of contracture of the inferior rectus muscle were revealed in 4 cases of strabismus that occurred after retrobulbar anesthesia. Pronounced increase in the lateral dimensions of the extraocular muscles was determined in 4 patients with TED, as well as in patients who had underwent BOD. Displacement of the lateral and medial rectus muscles into the formed bony windows with a change in the vector of their action was observed in patients who had underwent BOD. CONCLUSION: The data obtained with functional MSCT of the orbits in 34 patients allowed more accurate characterization of the oculomotor disorders and evaluation of the functional state of the extraocular muscles.

Inferior rectus displacement in heavy eye syndrome and sagging eye syndrome.

PURPOSE: To evaluate if there is a nasal displacement of the vertical rectus muscles in heavy eye syndrome (HES) and/or sagging eye syndrome (SES) compared with age-matched controls. METHODS: We reviewed the charts of all patients with the diagnosis of HES or SES who were seen at the University of California San Diego (UCSD) between the years 2008-2016 who underwent magnetic resonance imaging (MRI) of the brain and orbits. The control group included patients who had brain and orbital MRIs at UCSD in the absence of known pathology in the orbits or globes. Measurements were taken by 3 separate examiners for all groups. RESULTS: Twenty-four patients (16 with SES and 8 with HES) and 24 age-matched controls were retrospectively reviewed. The superior rectus (SR) of patients with HES and SES was more nasally displaced from the midline compared with that of age-matched controls (p = 0.04, p = 0.03, respectively). The inferior rectus (IR) of patients with HES but not with SES was more nasally displaced from the midline compared with that of age-matched controls (p = 0.04, p = 0.62, respectively). In all groups, the IR nasal displacement from the midline was approximately double compared with the SR. CONCLUSIONS: There is a significant nasal displacement of the SR in HES and SES and IR in HES. The observed IR nasal displacement in HES is a new finding and may explain the residual hypotropia and/or esotropia following surgical interventions for HES not involving the IR.

Altered Brain Network Centrality in Patients with Adult Strabismus with Amblyopia: A Resting-State Functional Magnetic Resonance Imaging (fMRI) Study.

BACKGROUND The aim of this study was to explore potential changes in brain function network activity in patients with adult strabismus with amblyopia (SA) using the voxel-wise degree centrality (DC) method. MATERIAL AND METHODS We enrolled 15 patients with SA (6 males, 9 females) and 15 sex-matched healthy controls (HCs). All subjects completed resting functional magnetic resonance imaging scans. Independent-sample t tests and receiver operating characteristic (ROC) curves were used to assess DC value differences between groups, and Pearson correlation analysis was performed to evaluate correlations between DC-changed brain regions and clinical data of patients with SA. RESULTS Compared with the HC group, DC values that were lower in patients with SA included the left middle frontal gyrus and bilateral angular gyri. Increases were observed in the left fusiform gyrus, right lingual gyrus, right middle occipital gyrus, right postcentral gyrus, and left paracentral lobule. However, DC values were not correlated with clinical manifestations. ROC curve analysis showed high accuracy. CONCLUSIONS We found abnormal neural activity in specific brain regions in patients with SA. Specifically, we observed significant changes in DC values compared to HCs. These changes may be useful to identify the specific mechanisms involved in brain dysfunction in SA.

[Paying attention to the application of imaging examination in strabismus].

There are many pathogenic factors of strabismus. In addition to the changes of alignment and ocular movement, there may be abnormal pathways and development of extraocular muscles, abnormalities of orbital and intraorbital connective tissue, paralysis of cranial nerves (oculomotor nerve, trochlear nerve, and abductor nerve), and nuclear and supranuclear lesions, accompanied by other cerebral dysplasia sometimes. In recent years, advances in imaging technology and its application in the professional field of strabismus have made it possible to clearly observe the eye, orbital, intracranial, and innervation changes, which is helpful to clarify the etiology of strabismus and extraocular muscle-related diseases, and to provide a basis for the diagnosis and treatment of strabismus. Strabismus specialists should learn and pay attention to the application of imaging examination, so as to achieve in-depth understanding and accurate treatment. (Chin J Ophthalmol, 2020, 56: 166-170).

Zygomatic dental implant induced orbital fracture and inferior oblique trauma.

A 51-year-old female underwent four upper zygomatic dental implants (ZI) and one upper and four lower conventional implants. Immediately postoperatively, the patient had pain and diplopia upon manual elevation of the edematous eyelid. Panoramic x-ray showed a malpositioned right upper ZI, requiring removal of the right upper ZI the following day. The patient had delayed referral to ophthalmology one month later for persistent diplopia. Computed tomography scan and magnetic resonance imaging demonstrated a right inferolateral fracture with fibrosis surrounding the inferior oblique muscle. Clinical exam showed right lower eyelid retraction, right hypotropia, and inability to elevate in adduction, consistent with a right inferior oblique paresis. Surgical exploration revealed incarceration of lid and orbital tissue into the fracture. After repositioning of the prolapsed tissue, a high-density porous polyethylene implant was placed for fracture repair. The inferior fornix was reconstructed with amniotic membrane and 5-fluorouracil was injected into the scar tissue. Six months later, the patient underwent strabismus surgery with resolution of symptoms.

[Application of MRI in the etiological diagnosis of special forms of strabismus].

Objective: To explore the imaging features of patients with special forms of strabismus and summarize the subtypes by using MRI imaging techniques. Methods: A retrospective case series study. Among the patients who visited the Beijing Tongren Hospital between 2006 and 2016, 1 113 patients were identified with special forms of strabismus after complete ophthalmic and orthoptic evaluations. These patients were further evaluated using several types of high-resolution MRI techniques of the oculomotor nerves in the brain, the cavernous sinus, and the orbits. Results: Among the 1 113 patients, 818 patients (73.5%) were identified with MRI abnormal conditions, and 295 patients (26.5%) were identified with MRI normal conditions. Nine different disease types were identified in the studied populations, which included 257 patients (23.1%) with congenital cranial dysinnervation disorders, 209 patients (18.8%) with thyroid associated ophthalmopathy, and 169 patients (15.2%) with abnormalities of the extraocular muscles. Other diseases included orbital fractures (3.3%, 37 patients), intraorbital inflammations (2.7%, 30 patients), tumors (2.3%, 26 patients), injuries of medial rectus muscle after endoscopic sinus surgery (1.2%,13 patients), and lesions of cavernous sinus (2.0%, 22 patients). Additional 55 patients (4.9%) were identified with other causes such as high myopia fixed esotropia, and so on. Conclusion: Summarizing the common clinical characteristics and rules with the help of MRI can further clarify the etiology of special forms of strabismus, and accurately guide the diagnosis and treatment of strabismus. (Chin J Ophthalmol, 2019, 55: 361-368).

TOR1A variants cause a severe arthrogryposis with developmental delay, strabismus and tremor.

See Ginevrino and Valente (doi:10.1093/brain/awx260) for a scientific commentary on this article. Autosomal dominant torsion dystonia-1 is a disease with incomplete penetrance most often caused by an in-frame GAG deletion (p.Glu303del) in the endoplasmic reticulum luminal protein torsinA encoded by TOR1A. We report an association of the homozygous dominant disease-causing TOR1A p.Glu303del mutation, and a novel homozygous missense variant (p.Gly318Ser) with a severe arthrogryposis phenotype with developmental delay, strabismus and tremor in three unrelated Iranian families. All parents who were carriers of the TOR1A variant showed no evidence of neurological symptoms or signs, indicating decreased penetrance similar to families with autosomal dominant torsion dystonia-1. The results from cell assays demonstrate that the p.Gly318Ser substitution causes a redistribution of torsinA from the endoplasmic reticulum to the nuclear envelope, similar to the hallmark of the p.Glu303del mutation. Our study highlights that TOR1A mutations should be considered in patients with severe arthrogryposis and further expands the phenotypic spectrum associated with TOR1A mutations.

Rectus Pulley Displacements without Abnormal Oblique Contractility Explain Strabismus in Superior Oblique Palsy.

PURPOSE: Using high-resolution magnetic resonance imaging (MRI), we investigated whether rectus pulleys are significantly displaced in superior oblique (SO) palsy and whether displacements account for strabismus patterns. DESIGN: Prospective case-control study. PARTICIPANTS: Twenty-four patients diagnosed with SO palsy based on atrophy of the SO muscle on MRI and 19 age-matched orthotropic control subjects. METHODS: High-resolution, surface coil MRI scans were obtained in multiple, contiguous, quasicoronal planes during monocular central gaze fixation. Pulley locations in oculocentric coordinates in the following subgroups of patients with SO palsy were compared with normal results in subgroups of patients with SO palsy: unilateral versus bilateral, congenital versus acquired, and isotropic (round) versus anisotropic (elongated) SO atrophy. Expected effects of pulley displacements were modeled using Orbit 1.8 (Eidactics, San Francisco, CA) computational simulation. MAIN OUTCOME MEASURES: Rectus pulley positions and ocular torsion. RESULTS: Rectus pulleys typically were displaced in SO palsy. In unilateral SO palsy, on average the medial rectus (MR) pulley was displaced 1.1 mm superiorly, the superior rectus (SR) pulley was displaced 0.8 mm temporally, and the inferior rectus (IR) pulley was displaced 0.6 mm superiorly and 0.9 mm nasally from normal. Displacements were similar in bilateral SO palsy, with the SR pulley additionally displaced 0.9 mm superiorly. However, the lateral rectus pulley was not displaced in either unilateral or bilateral SO palsy. The SR and MR pulleys were displaced in congenital SO palsy, whereas the IR and MR pulleys were displaced in acquired palsy. Pulley positions did not differ between isotropic and anisotropic palsy or between patients with cyclotropia of less than 7° versus cyclotropia of 7° or more. Simulations predicted that the observed pulley displacements alone could cause patterns of incomitant strabismus typical of SO palsy, without requiring any abnormality of SO or inferior oblique strength. CONCLUSIONS: Rectus pulley displacements alone, without abnormal oblique muscle contractility, can create the clinical patterns of incomitant strabismus in SO palsy. This finding supports accumulating evidence that clinical binocular misalignment patterns are not reliable indicators of contractile function of the SO muscle. Ocular torsion does not correlate with and thus cannot account for pulley displacements in SO palsy.

[The application of anterior segment optical coherence tomography in residual strabismus surgery].

OBJECTIVE: To evaluate the application of anterior segment optical coherence tomography (ASOCT) in surgical design for residual horizontal strabismus patients. METHODS: This article was a retrospective case series analysis. Total 20 residual strabismus patients (13 with residual exotropia and 7 with residual esotropia) in Eye Hospital of Wenzhou Medical University from Jan 2009 to Jan 2011 were studied. Routine strabismus examinations were completed preoperatively. The distance between insertion of horizontal rectus muscles and corneal limbus were measured with ASOCT preoperatively and calipers intraoperatively. Reoperational amount and method for residual strabismus patients were designed according to the limbus-insertion distance. The paired t test was used to compare the agreement between two methods of measurement of limbus-insertion distance. The cure rates of reoperation were analyzed. RESULTS: No statistical significance was observed between the measurements with ASOCT (7.7±1.7) mm and calipers (7.8±1.1)mm (t=-1.37, P=0.19). According to ASOCT image, the second surgical method was re-recession muscle for 4 patients; re-recession of original performed muscle combined with antagonist muscle resection for 10 patients and antagonist muscle resection combined with horizontal rectus muscle recession in fellow eye for 6 patients. All the surgical processes went on successfully, no severe intraoperative and postopereative complications were noted. Sixteen cases were cured (80%) . CONCLUSIONS: Horizontal rectus muscle evaluation with ASOCT preoperatively may benefit the choice of performed muscle, calculation of surgical amount, reduction of unnecessary surgical procedure and optimization second surgical design for residual strabismus patients. (Chin J Ophthalmol, 2016, 52: 568-573).

Postoperative magnetic resonance imaging of the inferior oblique muscle.

No previous imaging study has described the appearance of the inferior oblique muscle after surgery. It is unknown whether findings signifying prior myectomy or recession are recognizable on magnetic resonance (MR) imaging and how they might differ for the two procedures. After myectomy via a temporal approach, the cauterized muscle stump retracts into the medial orbit. How far it retracts and whether it reattaches to the globe remains unclear. To address these issues, orbital MR images were reviewed in 5 patients who had previously undergone inferior oblique myectomy or recession. In each case, the operated muscle exhibited subtle but telltale features, when compared with the normal, fellow inferior oblique. After myectomy, the inferior oblique still terminated lateral to the inferior rectus muscle and appeared closely apposed to the globe, although not necessarily attached to the sclera.

Agreement between intraoperative and anterior segment optical coherence tomography measurements of the extraocular muscle insertion distance in patients with previous strabismus surgery.

PURPOSE: To evaluate the agreement between anterior segment optical coherence tomography (AS-OCT) measurement of preoperative distance from the limbus to the horizontal rectus muscle insertion and intraoperative measurement in patients who have previously undergone strabismus surgery and required reoperation. METHODS: Subjects from two ophthalmological centers were included. Preoperative AS-OCT was used to measure the muscle insertion from the limbus, and intraoperative measurements were obtained using calipers. Interclass correlation coefficient and Bland-Altman agreement analysis were used. RESULTS: A total of 53 horizontal rectus muscles from 24 patients with previous strabismus surgery were analyzed: 27 medial rectus (MR) and 26 lateral rectus (LR) muscles, including both previously operated and previously unoperated muscles. Average of AS-OCT measurements of MR was 8.54 ± 2.42 mm and intraoperatively was 9.4 ± 3.09 mm. Average AS-OCT for LR was 8.32 ± 2.25 mm and intraoperatively was 9.34 ± 3.73 mm. 63% of MR muscles and 77% of LR muscles were within 1 mm between AS-OCT and intraoperative measurement. Spearman's correlation coefficient showed positive correlation between measures for both MR and LR muscles. The interclass correlation coefficient was 0.79 (95% CI, 0.56-0.90) for MR muscles and 0.70 (95% CI, 0.44-0.85) for LR muscles, with a good agreement. Agreement was better for muscles ≤10 mm from the limbus (which included both previously operated and unoperated muscles) than for muscles found >10 mm from the limbus. CONCLUSIONS: Good agreement was observed between the measurement of limbus-insertion distance obtained by AS-OCT and by intraoperative measurement, especially when the muscle insertion was ≤10 mm from the limbus.

A new method based on deep learning and image processing for detection of strabismus with the Hirschberg test.

Strabismus is a condition in which one or both eyes do not work in parallel or in harmony. People with strabismus have one eye looking straight ahead while the other eye looks inwards, outwards, upwards or downwards. This condition can affect both eyes. Strabismus is a common eye condition that affects about 4 % of the world's population. Tests such as Hirschberg, Cover and Krimsky are used to detect strabismus. In the Hirschberg test, a light source is held at a distance of 50 cm so that it falls on the centre of each eye. The horizontal and vertical distance between the centre of gravity of the light reflected from the cornea and the centre of the pupil indicates the degree of strabismus. In this study, deep learning and image processing algorithms are used to detect the eye, corneal reflection, iris and pupil on a patient's facial image. Based on the Hirschberg test, the horizontal and vertical shifts for both eyes were measured to determine the patient's degree of strabismus. In this way, the Hirschberg test used in strabismus screening was performed automatically by software. The correct detection of the pupil and the light reflected from the cornea by the algorithm means that the eye has been measured correctly. The software was tested on the facial images of 88 strabismic patients of different sexes and ages. 91 % of the 88 patients, or 80 patients, had their left eye measured correctly. 90 % of the 88 patients, or 79 patients, had their right eye measured correctly. The results for each eye obtained from the correct measurements were found to have an error of maximum ± 2°. This error is due to the fact that a real eye is in three-dimensional space, while the digital eye image is in two-dimensional space, and was only observed in the test results of some patients. This algorithm can be tested on patients of all ages and is not affected by morphological differences in the patients' faces. Successful results have been observed experimentally that this newly proposed method can be used in strabismus screening.

Assessment of retinal and choroidal microcirculation after unilateral recession-resection surgery for horizontal strabismus by swept-source optical coherence tomography angiography.

This study explored the possible hemodynamic changes of the retina and choroid after horizontal strabismus surgery using swept-source optical coherence tomography angiography (SS-OCTA). 32 eyes of 32 patients who underwent unilateral horizontal rectus muscle recession-resection surgery were included. SS-OCTA examinations were performed preoperatively and one week postoperatively. Several OCTA measurements were used, including vessel density (VD) of the superficial vascular complex (SVC), VD of the deep vascular complex (DVC), VD of the choriocapillaris (CC), choroidal vascular index (CVI) and choroidal thickness (CT). No significant change in VD of SVC, DVC, and CC was observed whereas CT increased significantly with CVI unchanged. Recession-resection surgery for horizontal strabismus seemed not to significantly influence the microcirculation of the retina and CC in the early postoperative period. However, choroidal thickening happened with a constant CVI probably due to the postoperative inflammation. Further studies are needed to investigate the long-term effects of unilateral recession-resection surgery for horizontal strabismus on the microcirculation of the retina and choroid.

Automated Mathematical Algorithm for Quantitative Measurement of Strabismus Based on Photographs of Nine Cardinal Gaze Positions.

This study presents an automated algorithm that measures ocular deviation quantitatively using photographs of the nine cardinal points of gaze by means of deep learning (DL) and image processing techniques. Photographs were collected from patients with strabismus. The images were used as inputs for the DL segmentation models that segmented the sclerae and limbi. Subsequently, the images were registered for the mathematical algorithm. Two-dimensional sclera and limbus were modeled, and the corneal light reflex points of the primary gaze images were determined. Limbus recognition was performed to measure the pixel-wise distance between the corneal reflex point and limbus center. The segmentation models exhibited high performance, with 96.88% dice similarity coefficient (DSC) for the sclera segmentation and 95.71% DSC for the limbus segmentation. The mathematical algorithm was tested on two cranial nerve palsy patients to evaluate its ability to measure and compare ocular deviation in different directions. These results were consistent with the symptoms of such disorders. This algorithm successfully measured the distance of ocular deviation in patients with strabismus. With complementation in the dimension calculations, we expect that this algorithm can be used further in clinical settings to diagnose and measure strabismus at a low cost.