Two novel CHN1 variants identified in Duane retraction syndrome pedigrees disrupt development of ocular motor nerves in zebrafish.

Duane retraction syndrome (DRS) is a rare congenital eye movement disorder causing by the dysplasia of abducens nerve, and has highly variable phenotype. MRI can reveal the endophenotype of DRS. Most DRS cases are sporadical and isolated, while some are familial or accompanied by other ocular disorders and systemic congenital abnormalities. CHN1 was the most common causative gene for familial DRS. Until now, 13 missense variants of CHN1 have been reported. In this study, we enrolled two unrelated pedigrees with DRS. Detailed clinical examinations, MRI, and the whole exome sequencing (WES) were performed to reveal their clinical and genetic characteristics. Patients from pedigree-1 presented with isolated DRS, and a novel heterozygous variant c.650 A > G, p. His217Arg was identified in CHN1 gene. Patients from pedigree-2 presented with classic DRS and abnormalities in auricle morphology, and the pedigree segregated another novel heterozygous CHN1 variant c.637 T > C, p. Phe213Leu. A variety of bioinformatics software predicted that the two variants had deleterious or disease-causing effects. After injecting of two mutant CHN1 mRNAs into zebrafish embryos, the dysplasia of ocular motor nerves (OMN) was observed. Our present findings expanded the phenotypic and genotypic spectrum of CHN1 related DRS, as well as provided new insights into the role of CHN1 in OMN development. Genetic testing is strongly recommended for patients with a DRS family history or accompanying systemic congenital abnormalities.

Clinical features and visual prognosis of very late-onset neuromyelitis optica spectrum disorder-related optic neuritis.

BACKGROUND: Very late-onset neuromyelitis optica spectrum disorder-related optic neuritis is limited to a few case reports. OBJECTIVE: To investigate the clinical features and visual prognosis of very late-onset neuromyelitis optica spectrum disorder-related optic neuritis. METHODS: This study evaluated 22 patients with first-onset optic neuritis and fulfilled the 2015 diagnosis criteria for neuromyelitis optica spectrum disorders. RESULTS: The mean age at optic neuritis onset was 73.91 ± 4.71 (range: 70-82) years with a female predominance (81.8%; ratio: 4.5:1). Antinuclear antibody seropositivity and seronegativity were identified in 12 (55.5%) and 10 (45.5%) patients, respectively. Severe visual loss persisted in 19 (19/42, 45.3%) eyes at the last follow-up. Although patients with antinuclear antibody seropositivity had a significantly higher frequency of attacks (P = 0.015), but they had a longer median time to reach severe visual loss (37 vs. 26 months; log-rank test, P = 0.023). Multivariate logistic regression analysis revealed antinuclear antibody seropositivity (hazard ratio = 4.849, 95% confidence interval: 1.309-17.965, P = 0.018) as a good predictor of visual acuity improvement. CONCLUSION: Patients with very late-onset neuromyelitis optica spectrum disorder-related optic neuritis may develop severe optic neuritis, and those with antinuclear antibody seronegativity have a similar clinical presentation but worse outcome than those with seropositivity.

Clinical and Cerebrospinal Fluid Characteristics in 55 Cases of Tolosa-Hunt Syndrome: A Retrospective Analytical Study.

BACKGROUND: Several case series of patients with Tolosa-Hunt syndrome have been described in the literature; however, few studies have focused on the cerebrospinal fluid (CSF) characteristics. This study aimed to analyse the CSF characteristics of patients with Tolosa-Hunt syndrome. METHODS: Fifty-five patients who fulfilled the 3rd Edition of the International Classification of Headache Disorders diagnostic criteria for Tolosa-Hunt syndrome were included in this study. We retrospectively analysed data on CSF parameters, imaging findings, and clinical characteristics of these patients. RESULTS: Oligoclonal bands (OBs) were detected in the CSF of 13 (13/44, 29.5%) patients. The sex ratio was balanced. The mean age at onset of Tolosa-Hunt syndrome was 46.9 ± 10.23 (range 22-72) years. Eight (8/13, 61.5%) patients had multiple cranial nerve palsies. Lesions limited to the cavernous sinus were found on magnetic resonance imaging in 7 (7/13, 53.8%) patients. OBs were significantly detected more frequently in patients whose samples were evaluated less than 30 days after the onset of this diseases (p = 0.026); however, there were no significant differences in the protein level (p = 0.360) and IgG synthesis rate (p = 0.614). CONCLUSIONS: The detection of OBs in the CSF of patients with Tolosa-Hunt syndrome was not rare. It would be interesting to follow-up patients with OBs to determine whether they eventually developed an otherwise more specific inflammatory diagnosis.

Correlation between extent of lacrimal gland prolapse and clinical features of thyroid-associated ophthalmopathy: a retrospective observational study.

BACKGROUND: Studies on the factors related to lacrimal gland prolapse (LGP) in patients with thyroid-associated ophthalmopathy (TAO) are limited. This study aimed to assess the factors associated with LGP on magnetic resonance imaging (MRI) and its relation to TAO activity . METHODS: Thirty-six patients (72 orbits) with inactive TAO (43 orbits, Clinical Activity Score [CAS] < 3) or active TAO (29 orbits, CAS ≥3) were investigated retrospectively. All patients underwent ophthalmic evaluation and orbital magnetic resonance imaging. The severity of LGP and proptosis and the extraocular muscle (EOM) volume were measured. LGP and related factors were assessed by correlational and linear regression analyses. The value of LGP for discriminating the activity of TAO was evaluated by receiver-operating characteristic curve analysis. RESULTS: The mean LGP was significantly higher in the active TAO group than in the inactive TAO group (P < 0.001). There were significant positive correlations between LGP severity and the CAS (r = 0.51, P < 0.001), proptosis (r = 0.72, P < 0.001), and EOM volume (superior rectus [r = 0.49, P < 0.001], inferior rectus [r = 0.47, P < 0.001], lateral rectus [r = 0.59, P < 0.001], medial rectus [r = 0.62, P < 0.001], superior oblique [r = 0.48, P < 0.001], and all EOMs [r = 0.59, P < 0.001]). Receiver-operating characteristic curve analysis revealed an LGP of 13.65 mm (area under the curve, 0.824; sensitivity, 79.3%; specificity, 81.4%) to be the cut-off value that differentiated active and inactive TAO. CONCLUSIONS: LGP measurements obtained from orbital magnetic resonance images were positively correlated with CAS, proptosis and EOM volume. The extent of LGP appears to be a good indicator of disease activity in patients with TAO.

Orbital Volume and Axial Length Development in Individuals Ages 12 to 60 Years With Congenital Microphthalmia: A Retrospective Cohort Study.

OBJECTIVE: To analyze the stimulating effect of axial length development on orbital volume development in patients (ages 12-60 years) with congenital microphthalmia. METHODS: This retrospective cohort study included 43 patients (86 eyes) with congenital microphthalmia. Three-dimensional images of the orbit were generated from past computed tomography scans, and digital orbital volume and axial length measurements were taken. The patients were divided into four age groups for analyses. Paired t tests and one-way analysis of variance tests were used to compare orbital volume and axial length between the affected and unaffected eyes. Pearson correlation analyses and scatter plots were used to investigate the correlations between age, orbital volume, and axial length in the affected and unaffected eyes. Linear regression analysis was used to determine the association between orbital volume and axial length. RESULTS: The mean orbital volume in the affected and unaffected eyes was 17.08 ±â€Š2.88 and 20.80 ±â€Š2.55 cm3, respectively. The mean axis length in the affected and the unaffected groups was 12.73 ±â€Š3.54 and 23.84 ±â€Š1.43 mm, respectively. Significant differences were observed among orbital (t = 13.538, P < 0.001) volume and axial length (t = 21.339, P < 0.001) in the affected and the unaffected groups. There were no significant differences in affected orbital volume (F = 0.527, P > 0.05), unaffected orbital volume (F = 1.628, P > 0.05), affected axial length (F = 0.946, P > 0.05), and unaffected axial length (F = 2.217, P > 0.05) among the four age groups. According to the Pearson correlations, there were no significant correlations between age and affected volume, unaffected volume, affected axis, and unaffected axis (r = 0.095, 0.097, 0.084, and 0.022, respectively; all P > 0.05). Orbital volume was moderately correlated with axial length in the affected and unaffected groups (r = 0.470 and 0.410, respectively; both P < 0.01). Linear regression analysis revealed that a 1 mm change in axis length was associated with a 0.38 cm3 and 0.73 cm3 change in orbital volume in the affected and unaffected groups, respectively. CONCLUSIONS: In individuals ages 12 to 60 years old with congenital microphthalmia, the effect of axis length on the orbital volume growth of the affected eye is only half that of the unaffected eye. The eyeball, orbital tissue, and craniofacial development all play an important role in the growth of orbital volume.

Different Characteristics of Orbital Soft Tissue Expansion in Graves Orbitopathy: Extraocular Muscle Expansion is Correlated to Disease Activity While Fat Tissue Volume With Duration.

This study aimed to describe the correlation between some clinical features and orbital soft tissue volume in Graves orbitopathy (GO). The authors collected computed tomography scans from 56 untreated GO patients and measured fat volume (FV), intraorbital and extraorbital FV (IFV, EFV), bony cavity volume (BV), and extraocular muscle volume (MV) of the 112 orbits by using Mimics software. The ratio of soft tissue volume and BV were used to eliminate the individual variations. Outcomes were compared among groups and were correlated with clinical data, including age, sex, clinical activity score, duration, serum TSH receptor antibody (TRAb) level, body mass index and smoking status. Multivariate linear regression showed that higher MV/BV is associated with higher CAS and TRAb level ( P< 0.001, 0.005, res p ectively). No relationship was found between MV/BV and duration, sex, age, and body mass index. IFV/BV was related to duration (ß=0.138, 95% confidence interval: 0.076-0.201, P <0.001), and did not correlate to clinical activity. IFV and MV are positively associated with exophthalmometry ( P =0.009, <0.001, respectively), while orbital bony volume (BV) is negatively correlated with exophthalmometry ( P =0.025). Results suggested TRAb level can impact the severity of GO mainly by affecting extraocular muscle rather than fat tissue. MV of GO is associated with disease activity, whereas IFV is correlated with duration and increases over time.

Diabetic Oculomotor Nerve Palsy Displaying Enhancement of the Oculomotor Nerve in the Orbit and Cavernous Sinus on MRI.

INTRODUCTION: Imaging data were scarce on diabetic oculomotor nerve palsy (ONP). Our study explored the MRI features and their clinical implications for diabetic ONP. METHODS: Fifty-nine patients with a clinical diagnosis of diabetic ONP were recruited from our department between January 2015 and December 2019. Orbital MRI was retrospectively analyzed, and follow-up scans were obtained for 5 patients. Based on the ocular motor nerve palsy scale, the difference in the scores on the first and last hospital days was defined as the improvement score and was used to assess the treatment effects in all. RESULTS: Thirty-eight (64.41%) patients presented thickening and enhancement of the cavernous segment and inferior division of the intraorbital segment of the ipsilateral oculomotor nerve, with the cisternal segment spared in all. After complete resolution of symptoms, follow-up MRI in 5 patients revealed that the enhancement was less obvious compared with the previous images. 6 patients in the enhancement group and 4 patients in the nonenhancement group were treated with 80 mg of methylprednisolone. Significant differences were not detected in the median improvement scores between patients with and those without corticosteroid use (p = 0.240). CONCLUSION: Thickening and enhancement of the unilateral oculomotor nerve were common imaging findings in diabetic ONP, and they persisted after complete resolution of symptoms in some patients. The cavernous segment and the inferior division of the intraorbital segment were simultaneously involved, and the cisternal segment was often spared. Refraining from corticosteroids was recommended even with nerve enhancement.

Primary optic neuropathy in Behçet's syndrome.

BACKGROUND: Primary optic neuropathy in Behçet's syndrome (PONBS) is limited to a few case reports. OBJECTIVE: To investigate the clinical features, magnetic resonance imaging (MRI) changes, and visual prognosis of PONBS. METHODS: Sixty-one patients who presented with first onset of optic neuritis and fulfilled the International Criteria for Behçet's Disease (ICBD) were evaluated. RESULTS: The female-to-male ratio was 1.7:1. No patient had other central nervous system (CNS) disease. In 67 eyes with optic nerve abnormalities on MRI scan, perineural enhancement around the orbital optic nerve (46 eyes, 68.7%) was significantly more frequent than was increased signal in the optic nerve itself (31 eyes, 46.3%; p = 0.000), typically with sunflower-like appearance on coronal view (33 eyes, 71.7%). Two patients (3.6%) relapsed during follow-up (median 12 months). Kaplan-Meier survival analysis estimated the cumulative risk of severe visual loss (⩽0.1) at 24 months was 14.7% in females versus 62.5% in males (hazard ratio (HR), 0.16; 95% confidence interval, 0.05-0.54). CONCLUSION: PONBS frequently presents with isolated optic neuropathy in females. The sunflower-like sign might be a distinctive MRI feature. Short-term recurrence is very rare. Males have a higher cumulative risk of severe visual loss.

[Measurement of orbital development in children from birth to 6 years of age].

OBJECTIVE: An evaluation of orbital development in children from birth to 6 years of age was conducted in order to provide normal reference values for clinical use. METHODS: Retrospective cohort study. By combining multi-section helical computerized tomography (CT) imaging with a computer-aided design system (BrainLAB, Munich, Germany; iPlan Cranial Software, version 2.5), we measured the orbital volume of 100 emergency children (200 eyes), who underwent computerized tomography (CT) scanning due to mild injury in Beijing Tongren Hospital and had normal CT findings. From birth to 6 years of age, according to the age of < 1 years of age for the treatment of 0 year old group, aged 1 years old and < 2 years old for 1 year old group, and so on, divided into 7 groups. Among the 50 male and female patients, the ages are 0-6 years. All of these were in order to analyze the relationship between the age and orbital volume with unary linear correlation and regression. The comparison of orbital volume between females and males was performed using two independent t-tests. Comparisons of bilateral orbital volumes were performed using a paired t-test. RESULTS: The average orbital volume of children was initially (12.57 ± 3.80) cm(3) at birth, and then increased to (19.34 ± 1.86) cm(3) at 6 years of age, with an average annual growth of 1.13 cm(3). There was a positive linear relationship between orbital volume and age in children from birth to 6 years of age, yielding the regression equation: Y (orbital volume) = 13.582 + 1.042 × X(age). There is no statistic difference on the orbital volume between boys and girls (t = 1.073, 0.533, 1.808, 1.039, 1.346, 0.983, 1.774, P > 0.05). In addition, no statistic difference was found between the left and right orbital volume (t = 1.059, P = 0.292). The growth curves for all groups almost overlapped with each other. CONCLUSIONS: There is a positive linear relationship between orbital volume and age in children from 0 to 6. The bilateral orbital volumes were almost the same. There is no statistic difference on the orbital volume between boys and girls.

[Brown syndrome: clinical and radiological correlation].

OBJECTIVE: Brown syndrome is characterized by limitation of elevation in adduction, with complex mechanisms involving muscle, tendon, and trochlea. Here, we investigated mechanisms of Brown syndrome by magnetic resonance (MR) imaging. METHODS: It was a retrospective case series study. Fourteen patients with unilateral Brown syndrome between 3 and 54 years of age (10 cases of congenital and 4 cases with acquired disease) were included in the study. All patients underwent complete ophthalmic and orthoptic evaluation. Imaging of the ocular motor nerves at the brainstem was performed on 3D-FIESTA sequence, the orbits were imaged with FSE T1, T2WI using surface coils. RESULTS: Nine of 10 with congenital Brown syndrome demonstrated hypoplasia of the superior oblique (SO) of the affected side. Abnormal low signal intensity in the trochlea area was found in one patient. Three of 4 acquired patients had a history of trauma and were demonstrated fracture of the trochlea, extensive scarring, and superior orbital fracture. One acquired case was demonstrated scarring of anterior part of the SO and hypoplasia of the posterior part. CONCLUSION: Brown syndrome consists of a series of diseases. Their clinical features are quite similar while their anatomical mechanism varies in numerous ways. Therefore, based on patient's individual pathophysiology, the management in Brown syndrome should be personalized.

Maternal germline mosaicism of kinesin family member 21A (KIF21A) mutation causes complex phenotypes in a Chinese family with congenital fibrosis of the extraocular muscles.

PURPOSE: To identify the causative mutation with its possible origin in a Chinese family with congenital fibrosis of extraocular muscles type 1 (CFEOM1) and to characterize the ocular phenotypes and lesions in the corresponding intracranial nerves. METHODS: Three affected siblings and their asymptomatic parents underwent comprehensive ophthalmic examinations and neuropathologic analysis involving magnetic resonance imaging (MRI). KIF21A, PHOX2A, and TUBB3 genes were sequenced on the leukocyte-derived DNA to detect variants. The disease-linked haplotype was analyzed using four microsatellite markers across the KIF21A locus. RESULTS: All three affected individuals displayed typical CFEOM1. MRI revealed complicated but consistent neuromuscular abnormalities in the two patients examined, including hypoplastic oculomotor nerves, complete absence of bilateral superior rectus muscles, and unilateral absence of the abducens nerve with marked atrophy of the corresponding lateral rectus muscle. A heterozygous hotspot mutation KIF21A c.2860C>T was identified in all patients, but it was absent in both parents. Haplotype analysis of the disease locus showed the likely maternal inheritance of the disease-associated haplotype to all three affected offspring, strongly suggesting maternal germline mosaicism of the mutation. CONCLUSIONS: Germline mosaicism of KIF21A c.2860C>T is likely to cause the high occurrence of this mutation in the population. This information may be useful for genetic counseling. KIF21A mutations can affect the abducens nerve and cause complete absence of the bilateral superior rectus muscles. MRI characterization of new CFEOM1 phenotypes would assist clinical management.

Two cases of Duane retraction syndrome with abnormal orbital structures.

Duane retraction syndrome (DRS) is a rare congenital nonprogressive restrictive strabismus. The absence/hypoplasia of the abducens nerve and the aberrant innervation of the lateral rectus muscle by the oculomotor nerve have been hypothesized as causes of DRS, although the phenomenon of globe retraction can also occur in the setting of mechanical factors, such as congenital abnormal orbital structures or orbital trauma. We present the cases of 2 DRS patients with absent abducens nerve and abnormal muscular bands connecting the superior rectus and inferior rectus muscles on the temporal side of the optic nerve.

Optic nerve lesion length is a biomarker of visual disability in the pre-chronic phase of Leber's hereditary optic neuropathy.

OBJECTIVE: The current research aims to investigate relationships between the optic nerve (ON) lesion length with visual function in the pre-chronic phase ( illness duration < 12 months) of LHON. METHODS: Orbital MRI was retrospectively analyzed for 45 patients with LHON in the pre-chronic phase. ON lesion length was measured by 2 trained independent readers and it was recorded as multiplication of the number of abnormal MRI slices and slice thickness on T2-STIR sequence in the coronal plane. Decimal visual acuity was converted to the logarithm of minimum angle of resolution. Intra-class correlation coefficients (ICCs) were used to assess intra- and inter-observer agreements. Pearson's correlation analysis and multivariate linear regression models were performed to analyze the correlations of the lesion length with best corrected visual acuity (BCVA) and visual field parameters. RESULTS: 81 afflicted eyes were selected. The ICCs for intra-observer and inter-observer analyses were 0.989 and 0.980 respectively. Both Pearson's correlation analysis and multivariate linear regression models indicated a significant positive correlation between the BCVA or mean deviation (MD) and ON lesion length (rBCVA=0.368, PBCVA=0.001; rMD=-0.269, PMD=0.045) with a coefficient of determination (R2) of 0.152 and 0.114 respectively adjusted for patients' sex, age of onset, onset of vision loss to performance of MRI, mitochondrial DNA mutations. CONCLUSION: ON length with T2-STIR hyperintensities was positively associated with both BCVA and MD, and it was suspected to be a biomarker of visual disability in the pre-chronic phase of LHON.

Difference of anterior and posterior orbital development in patients with congenital microphthalmia: a retrospective cohort study from China.

AIM: To evaluate volume differences between anterior and posterior orbit and demographic characteristics of Chinese patients with congenital microphthalmia. METHODS: A retrospective cohort study, involving 169 unilateral congenital microphthalmia patients aged between 1 and 57 years old was conducted. Three-dimensional images of the orbit were generated from past CT scans, and digital orbital volume comprehensive measurement was done. The measured data included orbital volume (OBV), posterior orbital volume (POV), orbital width (OBW), orbital height (OBH), orbital depth (OBD), and posterior orbital area ratio. RESULTS: Significant differences were observed among OBV, POV, OBW, OBH, and OBD of the affected and unaffected eyes in different age-based groups (all P<0.001). Among them, OBH had the greatest different. The mean microphthalmic to contralateral ratio (MCR) of OBV, POV, OBW, and OBH continuously increased from 1 to 3 years old, whereas the MCR of POV decreased from 3 to 17 years old. The MCR of OBD was not found to be correlated to age. There was no significant difference between OBV, POV, OBW, and OBH in ages from 13 years old to adulthood (all P>0.05). The difference in posterior orbital area ratio between the affected and unaffected groups was not statistically significant (P>0.05). CONCLUSION: OBH is maximally affected, whereas OBD is minimally affected by microphthalmia. Posterior orbital retardation began 2y prior to orbital retardation and occurred at 3 years old in the affected eye, suggesting that intervention therapy should be done before the age of 4.

Upper airway fat tissue distribution in subjects with obstructive sleep apnea and its effect on retropalatal mechanical loads.

OBJECTIVE: To validate the hypothesis that fat tissue accumulation adjacent to the upper airway contributes to a predisposition to obstructive sleep apnea (OSA), irrespective of body mass index (BMI), as well as investigate the effect of the volume of fat tissue on pharyngeal mechanical loads. METHODS: Fourteen subjects and 14 controls were enrolled in this study. Pharyngeal anatomy (the fat tissue volume in the retropalatal region and retroglossal region) were evaluated using magnetic resonance imaging. Whether the subjects had a segmental closing pressure higher than atmospheric pressure was determined by pharyngoscopy under general anesthesia. The difference in fat tissue distribution between subjects with OSA and BMI-matched controls was investigated. Fat tissue distributions in subjects with positive or negative segmental closing pressure were also compared. RESULTS: Significant differences occurred between controls and subjects with OSA in volumes of parapharyngeal fat pad (P = .001), fat of soft palate (P = .01), as well as proportion of the parapharyngeal fat pad to the volume of total lateral pharyngeal soft tissues (P = .004). The volume of pharyngeal cavity, neck circumference, and volume of subcutaneous fat tissues were not significantly different statistically. Volume of fat in soft palate (odds ratio 5.893) and parapharyngeal fat pad in retropalatal and retroglossal region (odds ratios 1.781 and 1.845) were significant predictors of OSA. The volume of fat in the soft palate (P = .003) and parapharyngeal fat pad (P = .002) was higher in participants with positive retropalatal closing pressure; participants with positive retroglossal closing pressure had increased volumes of the tongue (P = .02) and the parapharyngeal fat pad (P = .004). CONCLUSIONS: Patients with OSA have more fat tissue adjacent to the pharyngeal cavity than BMI-matched controls. Fats deposited around the upper airway may contribute to the collapsibility of retropalatal and retroglossal airway in both patients and controls.

Clinical and genetic characteristics of Chinese patients with congenital cranial dysinnervation disorders.

BACKGROUND: Congenital cranial dysinnervation disorders (CCDDs) are a group of diseases with high clinical and genetic heterogeneity. Clinical examinations combined with Magnetic resonance imaging (MRI) and whole exome sequencing (WES) were performed to reveal the phenotypic and genotypic characteristics in a cohort of Chinese CCDDs patients. RESULTS: A total of 122 CCDDs patients from 96 families were enrolled. All patients showed restrictive eye movements, and 46 patients from 46 families (47.9%, 46/96) were accompanied by multiple congenital malformations. Multi-positional high-resolution MRI was performed in 94 patients from 88 families, of which, all patients had hypoplasia of the cranial nerves except HGPPS patients and 15 patients from 15 families (17.0%,15/88) were accompanied by other craniocerebral malformations. WES was performed in 122 CCDDs patients. Ten pathogenic variants were detected in KIF21A, TUBB3, and CHN1 genes in 43 families. Three variants were unreported, including KIF21A (c.1064T > C, p.F355S), TUBB3 (c.232T > A, p.S78T) and CHN1 (c.650A > G, p.H217R). Of the 43 probands harboring pathogenic variants, 42 were diagnosed with Congenital Fibrosis of Extraocular Muscles (CFEOM) and one was Duane Retraction Syndrome (DRS). No definite pathogenic variants in known candidate genes of CCDDs were found in sporadic DRS, Möbius Syndrome (MBS) and Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) patients. The CFEOM patients harboring R380C, E410K and R262H variants in TUBB3 gene and F355S variant in KIF21A gene exhibited syndromic phenotypes. CONCLUSIONS: This study broadened the phenotypic and genotypic spectrums of CCDDs, and it was the largest clinical and genetic investigation for CCDDs patients from China. KIF21A and TUBB3 were the common pathogenic genes in Chinese CFEOM. MRI coupled with WES can provide a supportive diagnosis in patients with clinically suspected CCDDs.

[Vertical retraction syndrome caused by anomalous orbital structures].

OBJECTIVE: To described the clinical feature and MRI imaging of six children with vertical retraction syndrome. METHODS: Six children with unilateral vertical retraction syndrome between 15 months and 8 years of age, mean age was (5.01 ± 1.27) years old. Strabismus examination included diopter, prism diopters, eye movement examination, binocular vision and fundus examination. Imaging of the ocular motor nerves at the brainstem was performed in 0.8 mm thickness image planes using 3D-FIESTA sequence, the orbits were imaged with FSE T1, T2WI using surface coils, and within 2.0 mm thick planes. RESULTS: Four children showed hypertropia, characterized by limited depression, a light retraction of the globe during downward gaze and eyelid lag. The MRI imaging showed anomalous orbital structure in the superonasal quadrant that between medial rectus and superior rectus or adjacent to the superior rectus. Two children showed intermittent exotropia, characterized by limited elevation, retraction of the globe and narrowing of the palpebral fissure during upward gaze. The MRI imaging showed anomalous orbital structure was present in the inferotemporal quadrant, one originate in inferior rectus and another close to the lateral rectus. CONCLUSION: Anomalous orbital structures are a main cause of vertical retraction syndrome. The presence of specific unusual eye movement and MRI imaging may assist in diagnosis. When the eyelid lag was found since the early age, anomalous orbital structures were implied.

Evaluation of MR imaging findings differentiating cavernous haemangiomas from schwannomas in the orbit.

OBJECTIVE: It is important to distinguish between orbital cavernous haemangioma and schwannoma because the treatments of choice for the two tumours are different. The aim was to evaluate MR imaging findings distinguishing the two tumours. METHODS: Magnetic resonance imaging including T1- and T2-weighted imaging and contrast-enhanced MR imaging was performed in 43 patients with cavernous haemangiomas and 16 patients with schwannomas confirmed by pathology. Location, configuration, margins, signal intensity, homogeneity and enhancement pattern of the tumour were retrospectively evaluated. RESULTS: There was a significant difference between cavernous haemangiomas and schwannomas regarding the location, configuration and margins of the mass, signal intensity and homogeneity on T1- and T2-weighted imaging, the spread pattern of contrast enhancement, the enhancement pattern and the type of time-intensity curve (P<0.05). Markedly homogeneous hyperintensity signal on T2-weighted imaging and the spread pattern of the contrast enhancement favoured cavernous haemangioma rather than schwannoma (P<0.01). CONCLUSION: Cavernous haemangiomas and schwannomas have different MR imaging features that could be helpful in the differentiation between the tumours. The spread pattern of the contrast enhancement on dynamic contrast-enhanced MR imaging is the most reliable finding distinguishing cavernous haemangiomas from schwannomas.

Value of MR imaging in the differentiation of benign and malignant orbital tumors in adults.

PURPOSE: To prospectively evaluate magnetic resonance (MR) imaging including dynamic contrast-enhanced MR imaging in the differentiation of benign from malignant orbital masses and to evaluate which MR imaging features are most predictive of malignant tumors. MATERIALS AND METHODS: The study was approved by the institutional review board and signed informed consent was obtained. Nonenhanced, static, and dynamic contrast-enhanced MR imaging was performed in 102 adult patients with an orbital mass. Diagnosis was based on histologic findings. MR imaging features of benign and malignant orbital lesions were evaluated correlated with histological findings. Multivariate logistic regression analysis was employed to identify the best combination of MR imaging features that might be predictive of malignancy. RESULTS: Nonenhanced, static, and dynamic enhancement MR imaging was significantly superior to two other models in prediction of malignancy (p < 0.05). Multivariate logistic regression analysis identified that the most discriminating MR imaging features were isointense mass on T2-weighted imaging and a washout-type time-intensity curve for both observers. CONCLUSION: Nonenhanced, static, and dynamic enhancement MR imaging improved differentiation between benign and malignant orbital masses in adult patients.

[Theoretic explanation about visual disorder induced by fibrous dysplasia of skull: pressure disequilibrium between lamina cribrosa].

OBJECTIVE: To investigate the causes for changes in optic nerve head and visual impairment caused by fibrous dysplasia (FD) of optic canal stenosis. METHODS: A total of 12 FD patients, diagnosed by CT, received the fundus and optical coherence tomography (OCT). Those with FD involving optic canal underwent decompression. The examination of OCT showed that lamina cribrosa located at the top was the exposure factor for retinal pigment epithelium (RPE). There were decreased vision or edematous optic nerve and atrophic lesion. Odds ratio was calculated by Fisher's exact test. RESULTS: The examination of CT showed the results of optic canal stenosis caused by lesions involving 18 sides: 8-sides with normal vision. Among which, 6 showing that lamina cribrosa was located below RPE and a lamina cribrosa plate near RPE at follow-up, 1 side OCT showing lamina cribrosa above RPE with normal optic nerve; a lateral lamina cribrosa was located above RPE with edematous optic nerve. Visual impairment at 10 sides, normal papillary 2 sides, atrophic papillary 8 sides, OCT showed that lamina cribrosa was located above RPE, postoperatively OCT showed that lamina cribrosa below with 7 sides having improved visual acuity. Fisher's exact test was performed (P = 0.000, odds ratio = infinity). CONCLUSION: The optic canal stenosis causes a rising pressure of lamina cribrosa zone to shift above RPE. The channel becomes distorted so as to squeeze and cut the ganglion cell axons of optic nerve, block the axoplasmic transport and result in blood circulation disorder. The above factors are the etiologies of visual impairments. Postoperatively lamina cribrosa zone pressure drops so that depressed lamina cribrosa and channel deformation recover and visual acuity improves.