ABSTRACT
OBJECTIVES: To evaluate the effect of inferior oblique (IO) myectomy on ocular torsion according to the absence of the trochlear nerve in unilateral congenital superior oblique palsy (UCSOP). METHODS: We retrospectively reviewed the clinical data of patients who had been diagnosed with UCSOP and underwent ipsilateral IO myectomy (n = 43). Patients were classified into the present and absent groups according to the absence of the trochlear nerve and superior oblique hypoplasia on magnetic resonance imaging (MRI). For quantitative analysis of ocular torsion, disc-fovea angles (DFA) were collected in both eyes using fundus photographs taken within three months before surgery and one month after surgery. RESULTS: DFA of the paretic eye did not differ according to the absence of the trochlear nerve (9.4±5.6° in the present group vs. 11.0±5.4° in the absent group, p = 0.508). However, the present group had a larger DFA in the non-paretic eye than the absent group (14.1±6.7° in the present group vs. 8.0±5.0° in the absent group, p = 0.003). The change of ocular torsion after IO myectomy in the paretic eye was -5.3±3.7° in the present group and -4.8±3.5° in the absent group, respectively (p = 0.801). In the non-paretic eye, the change in DFA was -1.5±3.0° in the present group, which was larger than that in the absent group (0.7±2.6°, p = 0.047). In the multivariate analysis, the change in DFA was correlated with only the preoperative DFA (standardized ß = -0.617, p<0.001 in the paretic eye, and standardized ß = -0.517, p<0.001 in the non-paretic eye). CONCLUSIONS: In the paretic eye, there was no significant difference in the change of ocular torsion between both groups, whereas in the non-paretic eye, the present group had a larger change in DFA after IO myectomy than the absent group. However, in the multivariable analysis, the change in ocular torsion was significantly correlated with preoperative excyclotorsion but not with the presence of the trochlear nerve itself.
Subject(s)
Strabismus , Trochlear Nerve Diseases , Humans , Trochlear Nerve/surgery , Trochlear Nerve/abnormalities , Trochlear Nerve/pathology , Trochlear Nerve Diseases/surgery , Trochlear Nerve Diseases/congenital , Trochlear Nerve Diseases/diagnosis , Retrospective Studies , Oculomotor Muscles/pathology , Fovea Centralis , Paralysis/pathology , Strabismus/surgery , Strabismus/pathologyABSTRACT
Strabismus is a significant cause of a decrease in the functional capabilities of the organ of vision, additionally, it leads to the deteriorating quality of life. Orbital factors and nervous system changes may play an important role in strabismus pathogenesis. There are few reports on binocular vision disorders in radiation-exposed persons.Functions of the external eyeball muscles might be disturbed based on the changed coordination process of subcortical nerve structures and due to altered metabolism. A carefully conducted research is necessary to clarify the possible pathogenesis of binocular vision disorders in radiation-exposed persons. OBJECTIVE: to assess the peculiarities of the development of strabismus and binocular vision disorders in people who were exposed to ionizing radiation in utero; to investigate the changes in distribution and appearance of myosin, dystrophin, and collagen IV between non-irradiated persons with normal binocular vision and patients with strabismus. MATERIALS AND METHODS: 583 persons, irradiated in utero because of the Chornobyl disaster were examined (at the time of examination average age was 11.3 ± 0.1 years). The control group - 808 people - Kyiv residents. Overall, 15 non-irradiated eyeball muscle samples were examined. 10 were from strabismus patients and 5 were controls. To evaluate morphological structure haematoxylin and eosin staining were used. For the detection of myosin, dystrophin, and collagen IV biotin-avidin (IMH) immunohistochemistry method was performed. Semi-quantitative grading method was used for the evaluation of immunoreactive structure appearance and local distribution. RESULTS: An increased frequency of divergent strabismus (p = 0.04190) and heterophoria (p = 0.002603) was found in the group exposed to prenatal (fetal) radiation because of the Chornobyl disaster compared to the control group. The relative risk of heterophoria was 5.08 (1.42 - 18.13). A decrease in dystrophin, myosin, and collagen IV positive structures was observed in non-irradiated strabismus-affected eyeball muscles compared to the control group. CONCLUSIONS: Detected changes indicate an increased probability in the development of strabismus in persons who had been exposed to fetal radiation. Non-irradiated strabismus-affected eyeball muscles are characterized by diminished myosin, dystrophin, and collagen IV immunohistochemical structures. Additionally, determined qualitative morphological changes in skeletal striated muscle fibers lead to the changed structural organization, indicating possible muscular dystrophy. Thereby, the presence of dystrophic processes in the eyeball muscles may play a significant role in the morphopatogenesis of strabismus. Further morphological studies are necessary to clarify the development of binocular vision disorder and the methods of their correction. These studies would be especially important to populations that were exposed to radiation.
Subject(s)
Chernobyl Nuclear Accident , Prenatal Exposure Delayed Effects , Strabismus , Vision, Binocular , Child , Female , Humans , Pregnancy , Collagen , Dystrophin , Oculomotor Muscles/pathology , Pilot Projects , Quality of Life , Strabismus/etiology , Strabismus/diagnosis , Strabismus/pathology , Vision, Binocular/physiologyABSTRACT
Purpose: Although the three-step test (3ST) is typically used to diagnose superior oblique palsy (SOP), sagging eye syndrome (SES) has clinical similarities. We sought to determine if alignment measurements can distinguish unilateral SOP from hypertropia in SES. Methods: We studied hypertropic subjects who underwent surface-coil magnetic resonance imaging (MRI) demonstrating either SO cross-section reduction indicative of congenital or acquired palsy (SOP group) or lateral rectus muscle sag (SES group). Alignment was measured by Hess screen and prism-cover testing. Multiple supervised machine learning methods were employed to evaluate diagnostic accuracy. Rectus pulley coordinates were determined in SES cases fulfilling the 3ST. Results: Twenty-three subjects had unilateral SOP manifested by SO atrophy. Eighteen others had normal SO size but MRI findings of SES. Maximum cross-section of the palsied SO was much smaller than contralaterally and in SES (P < 2 × 10-5). Inferior oblique cross-sections were similar in SOP and SES. In both SOP and SES, hypertropia increased in contralateral and decreased in ipsilateral gaze and was greater in ipsilateral than contralateral head tilt. In SES, nine subjects (50%) fulfilled the 3ST and had greater infraplacement of the lateral than medial rectus pulleys in the hypotropic orbit. Supervised machine learning of alignment data distinguished the diagnoses with areas under the receiver operating curves up to 0.93, representing excellent yet imperfect differential diagnosis. Conclusions: Because the 3ST is often positive in SES, clinical alignment patterns may confound SES with unilateral SOP, particularly acquired SOP. Machine learning substantially but imperfectly improves classification accuracy.
Subject(s)
Strabismus , Trochlear Nerve Diseases , Humans , Oculomotor Muscles/pathology , Orbit , Paralysis/complications , Paralysis/pathology , Retrospective Studies , Strabismus/diagnosis , Strabismus/pathology , Syndrome , Trochlear Nerve Diseases/complications , Trochlear Nerve Diseases/diagnosisABSTRACT
Apocrine hidrocystomas are benign cystic tumors derived from apocrine sweat glands; they are most commonly located in the skin of the head and neck regions. Ophthalmic occurrences typically appear at the lash line and canthi of the eyelid, although rare instances have been described in the conjunctiva, caruncle, and orbit. The authors illustrate an exceptional instance of a mobile episcleral cyst in a 12-year-old girl that developed about 2 years following strabismus surgery. The cyst was located anterior to the insertion of the left medial rectus and was excised in response to the patient's complaints of irritation. Histopathology of the excised specimen displayed an empty cyst lined by a double layer of cuboidal epithelium with the inner layer exhibiting apical decapitation secretion. Confirmatory immunohistochemistry demonstrated reactivity of both layers with CK7 and the outer myoepithelial layer with D2-40. Postoperative and traumatic cysts formed after interruption of the bulbar conjunctiva are usually conjunctival cysts lined by stratified squamous nonkeratinizing epithelium.
Subject(s)
Cysts , Hidrocystoma , Strabismus , Sweat Gland Neoplasms , Apocrine Glands/pathology , Child , Cysts/diagnosis , Cysts/etiology , Cysts/pathology , Female , Hidrocystoma/diagnosis , Hidrocystoma/pathology , Humans , Strabismus/pathology , Sweat Gland Neoplasms/diagnosis , Sweat Gland Neoplasms/pathology , Sweat Gland Neoplasms/surgeryABSTRACT
The rostral mesencephalon may influence ocular motility in the vertical, horizontal, and torsional trajectories through intricate supranuclear, internuclear, and infranuclear neural networks. Strategic unilateral midbrain lesions may result in contralateral horizontal gaze palsy with saccadic failure due to combined interruption of supranuclear corticofugal fibers from the frontal eye field and colliculofugal fibers from the superior colliculus. In this article, we report a patient who sustained combined vertical and horizontal gaze deficits after a single infarct involving the mesodiencephalic junction. The neural substrate for each deficit is briefly discussed in light of clinical findings. This case presented a triad of three distinct syndromes of horizontal gaze paresis, vertical one-and-a-half syndrome, and pseudoabducens palsy due to damage of nuclear and supranuclear projections within the rostral mesencephalon. This combination was due to a single embolic infarct in the territory of the posterior thalamosubthalamic artery (artery of Percheron) that arises at the basilar bifurcation. Coexistence of these phenomena exemplified how rostral midbrain lesions may affect ocular motility in the vertical, horizontal, and torsional planes, along with disruption of normal vergence control.
Subject(s)
Magnetic Resonance Imaging , Strabismus , Humans , Infarction/pathology , Mesencephalon/blood supply , Mesencephalon/pathology , Paralysis/pathology , Paresis , Strabismus/pathologyABSTRACT
PURPOSE: Establishing the reliability of a new method to check the mean retinal and choroidal reflectivity and using it to find retinal and choroid changes in amblyopia. METHODS: Design: Retrospective case-control. Population: 28 subjects of which 10 were healthy controls (20 eyes): 8 with refractive errors, 1 with strabismus, and 1 with both. 18 patients with unilateral amblyopia included: 7 anisometropic, 6 isoametropic, 1 strabismic, and 4 combined. Mean participants' age: 13.77 years ± 10.28. Observation procedures: SD-OCT and ImageJ. Main outcome measure: mean reflectivity of retinal and choroid layers. Amblyopic, fellow, and healthy eyes were compared. RESULTS: The method of measuring reflectivity is good to excellent reliability for all regions of interest except the fourth. The mean reflectivity of the choriocapillaris and Sattler's layer in amblyopic eyes were significantly lower than in healthy eyes (p = 0.003 and p = 0.008 respectively). The RNFL reflectivity was lower than that of fellow eyes (p = 0.025). Post-hoc pairwise comparisons showed statistically significant differences between amblyopic and healthy eyes for choriocapillaris (p = 0.018) and Sattler's (p = 0.035), and between amblyopic and fellow eyes for RNFL (p = 0.039). CONCLUSION: A decrease in reflectivity of the choriocapillaris and Sattler's in amblyopic compared to healthy eyes, and a decrease in reflectivity of the RNFL in the amblyopic compared to fellow eyes, indicate that the pathophysiology is partly peripheral and might be bilateral.
Subject(s)
Amblyopia/diagnostic imaging , Anisometropia/pathology , Eye/diagnostic imaging , Retina/diagnostic imaging , Adolescent , Adult , Amblyopia/pathology , Anisometropia/diagnostic imaging , Child , Child, Preschool , Choroid/diagnostic imaging , Choroid/physiology , Choroid/ultrastructure , Eye/ultrastructure , Female , Humans , Male , Middle Aged , Nerve Fibers/pathology , Nerve Fibers/ultrastructure , Pilot Projects , Retina/pathology , Retina/ultrastructure , Retinal Ganglion Cells/pathology , Strabismus/diagnostic imaging , Strabismus/pathology , Tomography, Optical Coherence , Visual Acuity/physiology , Young AdultABSTRACT
The study aims to determine the prevalence of strabismus and its risk factors among school children in Hong Kong. This is a cross-sectional study involving 6-8 year old children from different districts in Hong Kong. 4273 children received comprehensive ophthalmological examination, cycloplegic auto-refraction, best corrected visual acuity (BCVA), anterior segment examination, cover/uncover test, ocular motility, and fundus examination. Demographic information, pre- and post- natal background, parental smoking status, and family history of strabismus were obtained through questionnaires. Strabismus was found among 133 children (3.11%, 95% CI 2.59-3.63%), including 117 (2.74%) exotropia and 12 (0.28%) esotropia cases (exotropia-esotropia ratio: 9.75:1). There was no significant difference in prevalence across age (6-8 years) and gender. Multivariate analysis revealed associations of strabismus with myopia (≤ - 1.00D; OR 1.61; 95% CI 1.03-2.52; P = 0.037) hyperopia (≥ + 2.00D; OR 2.49; 95% CI 1.42-4.39; P = 0.002), astigmatism (≥ + 2.00D; OR 2.32; 95% CI 1.36-3.94; P = 0.002), and anisometropia (≥ 2.00D; OR 3.21; 95% CI 1.36-7.55; P = 0.008). Other risk factors for strabismus included maternal smoking during pregnancy (OR 4.21; 95% CI 1.80-9.81; P = 0.001), family history of strabismus (OR 6.36; 95% CI 2.78-14.50, P < 0.0001) and advanced maternal age at childbirth (> 35 years; OR 1.65; CI 1.09-2.49, P = 0.018). The prevalence of strabismus among children aged 6-8 years in Hong Kong is 3.11%. Refractive errors, family history of strabismus and maternal smoking history during pregnancy are risk factors. Early correction of refractive errors and avoidance of maternal smoking during pregnancy are potentially helpful in preventing strabismus.
Subject(s)
Anisometropia/epidemiology , Esotropia/epidemiology , Exotropia/epidemiology , Strabismus/epidemiology , Anisometropia/diagnosis , Anisometropia/diagnostic imaging , Anisometropia/pathology , Child , Esotropia/diagnosis , Esotropia/diagnostic imaging , Esotropia/pathology , Exotropia/diagnosis , Exotropia/diagnostic imaging , Exotropia/pathology , Female , Hong Kong/epidemiology , Humans , Male , Refraction, Ocular/physiology , Refractive Errors/diagnosis , Refractive Errors/diagnostic imaging , Refractive Errors/epidemiology , Refractive Errors/physiopathology , Risk Factors , Strabismus/diagnosis , Strabismus/diagnostic imaging , Strabismus/pathology , Vision Tests , Visual Acuity/physiologyABSTRACT
In a consanguineous Pakistani kinship afflicted with mild to moderate intellectual disability (ID), mild lissencephaly, brain atrophy and skeletal anomalies, we detected homozygous CRADD c.2T > G (p.Met1?) and USP44 c.873_886delinsT (p.Leu291Phefs*8), two good candidates 1.85-Mb apart that segregated with the disorder. Biallelic damaging variants in CRADD cause recessive mental retardation-34 (MRT34; MIM 614499) with mild to moderate ID, "thin" lissencephaly, and variable megalencephaly and seizures. For USP44, only a single ID family has been reported with a homozygous deleterious variant, which is the same as the variant we detected. In affected individuals we present, at ages 29-32 years, clinical findings are similar yet not fully concordant with phenotypes for either gene considering the skeletal findings, and ID is not as severe as would be expected for defects in two genes with additive effect. Some variable CRADD-related features such as language impairment and seizures are not observed in the presented family. The presence of the two variants in the family is a very rare example of familial linked homozygous variants, and whether the damaging USP44 variant contributed to the disease in the family we present is not clear. As for the skeletal findings, facial dysmorphism and digestive problems, we did not find a candidate variant. This study is an example of both clinical variation and difficulty in variant detection and evaluation. Our findings highlight that even an extensive exome sequence analysis can fail to fully uncover the complex molecular basis of a syndrome even if potentially causative variants are identified.
Subject(s)
CRADD Signaling Adaptor Protein/genetics , Developmental Disabilities/genetics , Intellectual Disability/genetics , Lissencephaly/genetics , Musculoskeletal Abnormalities/genetics , Strabismus/genetics , Ubiquitin Thiolesterase/genetics , Adult , Consanguinity , Developmental Disabilities/pathology , Female , Humans , Intellectual Disability/pathology , Lissencephaly/pathology , Male , Musculoskeletal Abnormalities/pathology , Mutation , Pedigree , Strabismus/pathology , SyndromeABSTRACT
Dual-specificity tyrosine phosphorylation-regulated kinase 1A or DYRK1A, contributes to central nervous system development in a dose-sensitive manner. Triallelic DYRK1A is implicated in the neuropathology of Down syndrome, whereas haploinsufficiency causes the rare DYRK1A-related intellectual disability syndrome (also known as mental retardation 7). It is characterised by intellectual disability, autism spectrum disorder and microcephaly with a typical facial gestalt. Preclinical studies elucidate a role for DYRK1A in eye development and case studies have reported associated ocular pathology. In this study families of the DYRK1A Syndrome International Association were asked to self-report any co-existing ocular abnormalities. Twenty-six patients responded but only 14 had molecular confirmation of a DYRK1A pathogenic variant. A further nineteen patients from the UK Genomics England 100,000 Genomes Project were identified and combined with 112 patients reported in the literature for further analysis. Ninety out of 145 patients (62.1%) with heterozygous DYRK1A variants revealed ocular features, these ranged from optic nerve hypoplasia (13%, 12/90), refractive error (35.6%, 32/90) and strabismus (21.1%, 19/90). Patients with DYRK1A variants should be referred to ophthalmology as part of their management care pathway to prevent amblyopia in children and reduce visual comorbidity, which may further impact on learning, behaviour, and quality of life.
Subject(s)
Central Nervous System/abnormalities , Central Nervous System/pathology , Intellectual Disability/genetics , Optic Nerve Diseases/genetics , Optic Nerve/abnormalities , Protein Serine-Threonine Kinases/genetics , Protein-Tyrosine Kinases/genetics , Central Nervous System/growth & development , Central Nervous System/metabolism , Child , Child, Preschool , Down Syndrome/genetics , Down Syndrome/pathology , Eye/pathology , Eye Abnormalities/genetics , Eye Abnormalities/pathology , Female , Haploinsufficiency/genetics , Humans , Infant , Intellectual Disability/pathology , Male , Middle Aged , Optic Nerve/pathology , Optic Nerve Diseases/pathology , Refractive Errors/genetics , Refractive Errors/pathology , Strabismus/genetics , Strabismus/pathology , Dyrk KinasesABSTRACT
3MC syndromes are rare heterogeneous autosomal recessive conditions previously designated as Mingarelli, Malpuech, Michels, and Carnevale syndromes, characterized by dysmorphic facial features, facial clefts, growth restriction, and intellectual disability. 3MC is secondary to mutations in the MASP1, MASP3, COLEC11, and COLEC10 genes. The number of patients with 3MC syndrome with known mutations in the COLEC11 or MASP1 is, to date, less than 50. At the time this case presented (2015), the only gene identified in Online Mendelian Inheritance in Man to be associated with 3MC syndrome was MASP1. We present, to the best of our knowledge, the first prenatal report of 3MC syndrome, secondary to a homozygous variant in MASP1. Fetal findings included bilateral cleft lip and palate, abnormality of the sacral spine, a right echogenic pelvic kidney, and brachycephaly. 3MC syndrome should be considered as part of the differential diagnosis when fetal ultrasound detects facial clefts and spinal defects, as the risk of recurrence is significant and a molecularly confirmed diagnosis allows for alternate reproductive options.
Subject(s)
Abnormalities, Multiple/genetics , Cleft Lip/genetics , Intellectual Disability/diagnosis , Mannose-Binding Protein-Associated Serine Proteases/genetics , Abdominal Muscles/abnormalities , Abdominal Muscles/pathology , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/pathology , Blepharoptosis/genetics , Blepharoptosis/pathology , Cleft Lip/diagnosis , Cleft Lip/pathology , Cleft Palate/genetics , Cleft Palate/pathology , Craniofacial Abnormalities/genetics , Craniofacial Abnormalities/pathology , Craniosynostoses/genetics , Craniosynostoses/pathology , Cryptorchidism/genetics , Cryptorchidism/pathology , Face/abnormalities , Female , Hip Dislocation, Congenital/genetics , Hip Dislocation, Congenital/pathology , Humans , Intellectual Disability/genetics , Intellectual Disability/pathology , Male , Mutation/genetics , Pregnancy , Strabismus/genetics , Strabismus/pathologyABSTRACT
Recent reports confirm innervational compartments of select rectus extraocular muscles as well as the superior oblique.1 Histopathological and orbital imaging studies demonstrate well defined compartmental innervation of the horizontal rectus muscles with less differentiation in the vertical rectus muscles. Acquired vertical misalignment not associated with cyclovertical muscle dysfunction has been associated with horizontal rectus muscle compartment dysfunction. Pattern and other forms of strabismus have been associated with segmental or compartmental abnormal innervation of the extraocular muscles. Taking advantage of segmental function and innervation, selective weakening and strengthening procedures have been used to treat patients with incomitant near/distance disparities, incomitant vertical and torsional strabismus, and patients with A- and V-pattern strabismus.
Subject(s)
Abducens Nerve Diseases/pathology , Compartment Syndromes/pathology , Oculomotor Muscles/innervation , Strabismus/pathology , HumansABSTRACT
BACKGROUND: The purpose of this study was to determine what craniometric changes occur to both orbits of unicoronal craniosynostosis patients undergoing fronto-orbital advancement and remodeling, and which of these changes are associated with new onset of postoperative strabismus. METHODS: A retrospective analysis was performed of the preoperative and postoperative orbits of 24 unicoronal craniosynostosis patients and the orbits of 24 control subjects, totaling 144 orbits. Eight parameters were evaluated using multivariate logistic regression analysis. One of the parameters was modified orbital index, an indicator of severity of harlequin deformity. RESULTS: Significant differences in orbital dimensions and angles were present bilaterally in unicoronal craniosynostosis orbits when compared to controls. Fronto-orbital advancement and remodeling increased the ipsilateral unicoronal craniosynostosis orbital volume from 13,184 ± 2003 mm to 16,220 ± 2323 mm (p < 0.001). Ipsilateral horizontal cone angles were increased from 48 ± 5 degrees to 54 ± 7 degrees (p = 0.004). Ipsilateral vertical cone angles were decreased from 73 ± 8 degrees to 66 ± 10 degrees (p = 0.003). Ipsilateral modified orbital index improved from 0.83 ± 0.06 to 0.88 ± 0.06 (p = 0.003). Three of the 19 unicoronal craniosynostosis patients developed transient postoperative strabismus. Logistic regression analysis displayed a strong significant association between new-onset strabismus and a change in modified orbital index with a coefficient of 30.84 ± 14.51 (p < 0.05). CONCLUSIONS: The orbital dysmorphology in unicoronal craniosynostosis is bilateral in nature, and it is not wholly treated with conventional fronto-orbital advancement and remodeling. The severity of ipsilateral orbital dysmorphology is correlated with the incidence of postoperative strabismus following conventional fronto-orbital advancement and remodeling. Future research is needed to develop strategies to mitigate the risk of development of strabismus in this group of patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.
Subject(s)
Craniosynostoses/complications , Frontal Bone/surgery , Orbit/surgery , Plastic Surgery Procedures/methods , Strabismus/etiology , Strabismus/surgery , Case-Control Studies , Female , Humans , Infant , Logistic Models , Male , Orbit/pathology , Retrospective Studies , Strabismus/pathologyABSTRACT
Strabismus is an ocular disorder characterized by partial or complete inability to keep eye alignment. It represents a very common ocular problem at ophthalmology clinics worldwide. The current study aimed to show the most encountered ultrastructural changes in extraocular muscles (EOMs) collected from patients with different forms of strabismus. Nine specimens of EOMs were collected from five patients during strabismus correction surgery and processed for light and electron microscopy examinations. Histologically, skeletal muscle fibers in normal EOMs appeared tight and normally arranged with clear striations. In strabismic muscles, the fibers appeared disarranged, and atrophied, swollen and disintegrated in some situations. By transmission electron microscopy, normal EOMs were formed of skeletal muscle fibers with intact basal membrane and sarcolemma, tightly aligned myofibrils with well-arranged sarcomeres, Z line and H zone, and normally distributed mitochondria. On the other hand, strabismic EOMs revealed vacuolation and degeneration of myofibrils, accumulation of lipid droplets, subsarcolemmal inclusions and clustering of mitochondria. EOMs obtained from a Down syndrome patient with V-pattern infantile esotropia showed extensive vacuolation and disintegration of myofibrils, and extra- and intracellular deposition of collagen fibers. Interestingly, some skeletal muscle cells exhibited features of autophagic cell death with a trial of engulfing process by neighboring cells. In conclusion, our study traces some characteristic ultrastructural changes in strabismic EOMs, most notably, extensive vacuolation, clustering of mitochondria, degeneration of myofibrils and autophagic changes. These changes might be emphasized as possibly secondary to strabismus.
Subject(s)
Oculomotor Muscles/pathology , Oculomotor Muscles/ultrastructure , Strabismus/pathology , Child , Child, Preschool , Female , Humans , Male , Microscopy, Electron, TransmissionABSTRACT
Strabismus refers to an abnormal alignment of the eyes leading to the loss of central binocular vision. Concomitant strabismus occurs when the angle of deviation is constant in all positions of gaze and often manifests in early childhood when it is considered to be a neurodevelopmental disorder of the visual system. As such, it is inherited as a complex genetic trait, affecting 2-4% of the population. A genome-wide association study (GWAS) for self-reported strabismus (1345 cases and 65,349 controls from UK Biobank) revealed a single genome-wide significant locus on chromosome 17q25. Approximately 20 variants across the NPLOC4-TSPAN10-PDE6G gene cluster and in almost perfect linkage disequilibrium (LD) were most strongly associated (lead variant: rs75078292, OR = 1.26, p = 2.24E-08). A recessive model provided a better fit to the data than an additive model. Association with strabismus was independent of refractive error, and the degree of association with strabismus was minimally attenuated after adjustment for amblyopia. The association with strabismus was replicated in an independent cohort of clinician-diagnosed children aged 7 years old (116 cases and 5084 controls; OR = 1.85, p = 0.009). The associated variants included 2 strong candidate causal variants predicted to have functional effects: rs6420484, which substitutes tyrosine for a conserved cysteine (C177Y) in the TSPAN10 gene, and a 4-bp deletion variant, rs397693108, predicted to cause a frameshift in TSPAN10. The population-attributable risk for the locus was approximately 8.4%, indicating an important role in conferring susceptibility to strabismus.
Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 6/genetics , Mutation , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide , Strabismus/genetics , Strabismus/pathology , Tetraspanins/genetics , Adult , Aged , Animals , Case-Control Studies , Child , Cohort Studies , Cyclic Nucleotide Phosphodiesterases, Type 6/metabolism , Female , Genome-Wide Association Study , Humans , Male , Mice , Middle Aged , Multigene Family , Nuclear Proteins/metabolism , Retina/metabolism , Risk Factors , Strabismus/metabolism , Tetraspanins/metabolism , Visual AcuityABSTRACT
PURPOSE: The management of A or V pattern deviation associated with esotropia can be challenging since the horizontal deviation changes with position of gaze. This study aimed to assess the effect of unilateral horizontal rectus surgery for the correction of horizontal deviation associated with A or V pattern in children with non-comitant infantile esotropia. METHODS: Twenty-seven children with infantile esotropia and A-V pattern, more than 10 and 15 prism diopters respectively, were included in this retrospective observational single-center study. Horizontal rectus surgery was performed on the most deviated eye under general anesthesia. The patients were divided into two groups: A pattern and V pattern. The outcome measures were change in the amount of pattern and rate of regression after surgery. The amount of pattern was characterized by the difference in esodeviation between upgaze and downgaze. RESULTS: Horizontal deviation at distance and near fixation decreased significantly (P<0.0001). Vertical gaze esotropia disparity decreased significantly (P=0.01 and P=0.0002 for A and V patterns respectively). A pattern esotropia was reported in only 2 (7%) cases after surgery compared to 9 (33%) before surgery. The number of subjects with V pattern esotropia decreased from 18 (67%) to 3 (11%) after surgery. CONCLUSIONS: The mechanisms involved in the pathophysiology of A and V patterns may not always be related to oblique muscle dysfunction. These findings suggest that unilateral horizontal rectus surgery may be an effective procedure to correct both horizontal deviation and A-V pattern in non-comitant infantile esotropia.
Subject(s)
Esotropia/congenital , Esotropia/surgery , Eye Abnormalities/surgery , Oculomotor Muscles/surgery , Ophthalmologic Surgical Procedures/methods , Adolescent , Child , Child, Preschool , Esotropia/epidemiology , Esotropia/pathology , Eye Abnormalities/epidemiology , Eye Abnormalities/pathology , Female , Humans , Male , Oculomotor Muscles/pathology , Retrospective Studies , Strabismus/congenital , Strabismus/epidemiology , Strabismus/pathology , Strabismus/surgery , Treatment Outcome , Vision, BinocularABSTRACT
PURPOSE: To develop a method to calculate the gaze angle in photographs and to determine its validity and reliability in real strabismus patients. METHODS: Photographs of eyes from 15 orthophoric subjects (n = 1,022) with known gaze angle and imaging distance were investigated with the help of a smartphone application developed by the authors. The application provided measurements of the distance from the geometrical center of the cornea to the light reflex (RD) and corneal diameter (CD). The RD/CD ratio of each gaze angle was recorded. To estimate the eyes' gaze angle, an equation to determine the best-fit line for the gaze angle data according to each RD/CD ratio was created. In a second clinical analysis, this equation was applied to photographs of real strabismus patients (n = 72), and the results were compared with measurements taken by a double-masked strabismus specialist. Separately, an equation was created to calculate the imaging distance using the given interpupillary distance. RESULTS: There was a high correlation between the real and estimated gaze angles (r = 0.990, P < 0.001). The mean error of the estimated gaze angle was found to be 0.03Δ ± 4.60Δ. There was a high correlation between the real and estimated imaging distance (r = 0.997, P < 0.001) and a high correlation between the measurements of the application and the specialist (r = 0.966, P < 0.001). The average error was -0.68 Δ ± 6.1Δ, and the reliability was high (Cronbach's α = 0.983). CONCLUSIONS: The application measured horizontal strabismus in photographs with high reliability.
Subject(s)
Photography/methods , Strabismus/pathology , Adolescent , Adult , Child , Child, Preschool , Esotropia/pathology , Exotropia/pathology , Fixation, Ocular/physiology , Healthy Volunteers , Humans , Mobile Applications , Reproducibility of Results , Smartphone , Young AdultABSTRACT
Ictal strabismus, sometimes associated with epileptic nystagmus, is an extremely rare epileptic phenomenon, suggestive of cortical involvement in monocular eye movement control. We describe a patient with ictal disconjugate contraversive horizontal eye deviation of cortical origin as the main clinical feature of a focal seizure. A 17-year-old, previously healthy woman had a seizure characterized by initial rightward conjugate eye deviation, followed by convergent strabismus due to adduction of the right eye towards the nose without conjugate left eye abduction (esotropia), forced leftward head deviation with impaired awareness, and subsequent evolution into a bilateral tonic-clonic seizure. Postictal and interictal neurological status were unremarkable; more specifically, neuro-ophthalmological examination revealed no nystagmus or altered eye motility. Ictal EEG showed a rhythmic theta activity over the right posterior temporal region, involving fronto-central regions when strabismus appeared. MRI showed cortical dysplasia in the right temporal lobe. Due to the low spatial resolution of scalp EEG, we could not identify with precision the symptomatogenic zone underlying ictal strabismus. However, the concomitant appearance of rhythmic theta activity over the right fronto-central region and the leftward head version with MRI perfusion sequences, showing cerebral blood flow increase in the right frontal eye field area, suggest involvement of the right frontal lobe. [Published with video sequence on www.epilepticdisorders.com].
Subject(s)
Cerebral Cortex , Seizures , Strabismus , Theta Rhythm/physiology , Adolescent , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Female , Humans , Magnetic Resonance Imaging , Seizures/complications , Seizures/diagnostic imaging , Seizures/pathology , Seizures/physiopathology , Strabismus/diagnostic imaging , Strabismus/etiology , Strabismus/pathology , Strabismus/physiopathologyABSTRACT
PURPOSE: To propose and validate a measure of medial wall bowing in thyroid eye disease (TED) and to assess the clinical correlates of bowing in TED. METHODS: In this cross-sectional cohort study, all patients affected with TED seen by a single specialist over a 2-year period were screened for study entry. Eligible participants were adults with clinical evidence of TED and either CT or MRI of the orbits. Exclusion criteria included prior history of decompression surgery and/or medical or other ophthalmic conditions that could alter the orbital anatomy. The primary outcome measure was prevalence of medial wall bowing. Secondary outcomes included the associations between medial wall bowing and exophthalmometry, diplopia, rectus muscle restriction, dysthyroid optic neuropathy (DON), strabismus, and quality of life. Medial wall bowing was defined as medial divergence of the medial wall from a straight line drawn between the anterior lacrimal crest and the middle of the optic canal and measured radiographically using axial images of the orbits. Volumetric analysis of bowing was performed on a sample of orbits with and without bowing. Volumetric and axial single slice measurements were compared. Bivariate statistics were performed. RESULTS: The final sample included 112 orbital images from 56 patients with TED. Medial wall bowing was found to be evident in 11.6% (n = 13/112) of orbits. Medial wall bowing was significantly associated with greater Hertel measurements, horizontal and vertical muscle restriction, ocular surface symptoms and Clinical Activity Score, as well as lower quality of life scores. Patients with demonstrable medial wall bowing were more likely to be affected by optic neuropathy, diplopia (Gorman score ≥ 1), strabismus, or horizontal muscle restriction. Analysis of the volume for medial wall bowing demonstrated that the height of the arc at the peak of bowing on an axial image of a 2-dimensional CT scan correlated highly with the total volume of bowing (r = 0.90, p < 0.001). CONCLUSIONS: The identification of medial wall bowing on CT or MRI is associated with clinical measures of disease severity, including diplopia and DON.
Subject(s)
Graves Ophthalmopathy/diagnosis , Adult , Aged , Cross-Sectional Studies , Diplopia/pathology , Female , Graves Ophthalmopathy/pathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Optic Nerve Diseases/pathology , Predictive Value of Tests , Quality of Life , Strabismus/pathology , Tomography, X-Ray Computed , Visual AcuitySubject(s)
Ectodermal Dysplasia 1, Anhidrotic/complications , Ectodysplasins/genetics , Strabismus/complications , Adult , Biopsy , Ectodermal Dysplasia 1, Anhidrotic/diagnosis , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodermal Dysplasia 1, Anhidrotic/pathology , Humans , Male , Sequence Deletion , Skin/pathology , Strabismus/diagnosis , Strabismus/genetics , Strabismus/pathologyABSTRACT
AIMS: To elucidate the intramuscular distribution and branching patterns of the abducens nerve in the lateral rectus (LR) muscle so as to provide anatomical confirmation of the presence of compartmentalization, including for use in clinical applications such as botulinum toxin injections. METHODS: Thirty whole-mount human cadaver specimens were dissected and then Sihler's stain was applied. The basic dimensions of the LR and its intramuscular nerve distribution were investigated. The distances from the muscle insertion to the point at which the abducens nerve enters the LR and to the terminal nerve plexus were also measured. RESULTS: The LR was 46.0 mm long. The abducens nerve enters the muscle on the posterior one-third of the LR and then typically divides into a few branches (average of 1.8). This supports a segregated abducens nerve selectively innervating compartments of the LR. The intramuscular nerve distribution showed a Y-shaped ramification with root-like arborization. The intramuscular nerve course finished around the middle of the LR (24.8 mm posterior to the insertion point) to form the terminal nerve plexus. This region should be considered the optimal target site for botulinum toxin injections. We have also identified the presence of an overlapping zone and communicating nerve branches between the neighboring LR compartments. CONCLUSION: Sihler's staining is a useful technique for visualizing the entire nerve network of the LR. Improving the knowledge of the nerve distribution patterns is important not only for researchers but also clinicians to understand the functions of the LR and the diverse pathophysiology of strabismus.