Successful resolution of stromal keratitis and uveitis using canakinumab in a patient with chronic infantile neurologic, cutaneous, and articular syndrome: a case study.

BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS) is a group of rare autoinflammatory diseases, and of these, chronic infantile neurologic, cutaneous, and articular/neonatal-onset multisystem inflammatory disease (CINCA/NOMID) syndrome has the most severe phenotype. Canakinumab, a monoclonal antibody that targets interleukin-1ß, has been shown to be an effective treatment for resolving systemic inflammation. However, its efficacy for treating ophthalmic symptoms of this disorder remains unclear. FINDINGS: A 64-year-old female reported episodes of nonpruritic urticaria, fever, aseptic meningitis, and bilateral sensorineural deafness. Her son had experienced similar symptoms. She was initially referred for ophthalmologic treatment for an infectious corneal ulcer. Examination of her right eye by slit lamp biomicroscopy showed diffuse conjunctival injection, corneal infiltrates, a corneal ulcer, and hypopyon. She was therefore treated aggressively with topical and systemic antibiotics in addition to antifungal medications. However, this was ineffective. Genetic analysis detected the heterozygous germline p.Asp303Asn mutation in the NLRP3 gene in both our patient and her son. She was therefore diagnosed with CINCA/NOMID syndrome based on her clinical manifestations. All of the patient's physical and ophthalmic symptoms were resolved within a few days after the initiation of canakinumab treatment. During an 18-month follow-up period, no adverse events or severe infections were observed. CONCLUSIONS: Our case report indicates that canakinumab is effective not only for the treatment of systemic inflammation but also for treating ophthalmic involvement, such as recurrent stromal keratitis and anterior uveitis.

Effects of oblique muscle surgery on the rectus muscle pulley.

PURPOSE: To determine the position of rectus muscle pulleys in Japanese eyes and to evaluate the effect of oblique muscle surgery on rectus muscle pulleys. METHODS: Quasi-coronal plane MRI was used to determine area centroids of the 4 rectus muscles. The area centroids of the rectus muscles were transformed to 2-dimensional coordinates to represent pulley positions. The effects of oblique muscle surgery on the rectus muscle pulley positions in the coronal plane were evaluated in 10 subjects with cyclovertical strabismus and, as a control, pulley locations in 7 normal Japanese subjects were calculated. RESULTS: The mean positions of the rectus muscle pulleys in the coronal plane did not significantly differ from previous reports on normal populations, including Caucasians. There were significant positional shifts of the individual horizontal and vertical rectus muscle pulleys in 3 (100%) patients with inferior oblique advancement, but not in eyes with inferior oblique recession and superior oblique tendon advancement surgery. The surgical cyclorotatory effect was significantly correlated with the change in the angle of inclination formed by the line connecting the vertical rectus muscles (p = 0.0234), but weakly correlated with that of the horizontal rectus muscles. CONCLUSIONS: The most important factor that affects the pulley position is the amount of ocular torsion, not the difference in surgical procedure induced by oblique muscle surgery.

Absence of relationship between oblique muscle size and bielschowsky head tilt phenomenon in clinically diagnosed superior oblique palsy.

PURPOSE: To study whether the variation in maximum oblique muscle size accounts for individual variation in the Bielschowsky head tilt phenomenon (BHTP) in clinically diagnosed superior oblique (SO) palsy. METHODS: Seventeen subjects with clinically diagnosed early-onset or idiopathic SO palsy and 14 normal subjects were enrolled in the study. Magnetic resonance imaging (MRI) in coronal and sagittal planes was used for quantitative morphometry of inferior oblique (IO) and SO muscles. Maximum cross-sectional area of the SO and IO cross section at the mid-inferior rectus crossing were determined in central gaze and compared with paretic eye hypertropia on ipsilesional versus contralesional head tilt. RESULTS: Mean (+/-SD) maximum SO cross section was 18.1 +/- 3.2 mm(2) in normal subjects, 14.2 +/- 6.8 mm(2) ipsilesional to SO palsy, and 19.2 +/- 4.5 mm(2) contralesional to SO palsy. The ipsilesional SO cross section was significantly smaller than the contralesional (P = 0.004) and normal (P = 0.01) ones. The mean IO cross section was 18.3 +/- 3.5 mm(2) in normal subjects, 21.3 +/- 7.9 mm(2) ipsilesional to SO palsy (P = 0.43), and 22.0 +/- 6.7 mm(2) contralesional to SO palsy (P = 0.26). Hyperdeviation varied with head tilt by 20.1 +/- 5.5 degrees in subjects with SO atrophy, and 10.3 +/- 5.6 degrees in subjects without SO atrophy (P = 0.003). Although oblique muscle cross sections did not correlate with BHTP, subjects with clinically diagnosed SO palsy segregated into groups exhibiting normal versus atrophic SO size. CONCLUSIONS: SO size does not account for the variation in BHTP in clinically diagnosed SO palsy, supporting the proposition that the BHTP is nonspecific for SO function.

Splitting of the extraocular horizontal rectus muscle in congenital cranial dysinnervation disorders.

PURPOSE: To analyze the horizontal rectus extraocular muscles (EOMs) by orbital magnetic resonance imaging (MRI) in patients with congenital cranial dysinnervation disorders that arises from abnormal development of cranial nerve nuclei or their axonal connections. DESIGN: Case series, retrospective analysis. METHODS: The morphology of the horizontal rectus EOMs was analyzed in orbital MRI on 4 patients with congenital oculomotor palsy, 26 with congenital superior oblique palsy, and five with Duane syndrome. Orbital imaging was performed by 1.5 tesla (T) and 3T MRI, and quasi-coronal and sagittal images perpendicular and parallel to the long axis of the orbit were obtained at slice thicknesses of 3 and 2 mm. RESULTS: The horizontal rectus EOMs were split in 4 of the 35 patients (11%). Splitting was observed in 2 of the five patients (40%) with Duane syndrome, one of the 26 patients (4%) with congenital superior oblique palsy, and 1 of the 4 patients (25%) with oculomotor palsy, but in none of the 6 normal subjects and 12 patients with acquired cranial nerve palsy. CONCLUSION: Since splitting of the horizontal rectus EOMs was noted in patients with congenital dysinnervation disorders, including Duane syndrome, Sevel's theory that the horizontal rectus EOMs develop from the superior and inferior mesodermal complexes is considered to be reasonable.

Displacement of the rectus muscle pulleys simulating superior oblique palsy.

PURPOSE: To investigate the structural basis of three cases of apparent superior oblique (SO) palsy caused by extraocular muscle (EOM) pulley heterotopy. METHODS: Three subjects were diagnosed as having decompensated idiopathic left SO palsy on the basis of misalignment in diagnostic gaze positions, response to the head tilt test, and results of the Hess screen test. Magnetic resonance imaging of the orbits in coronal planes was used to determine SO muscle size and contractility and to define the rectus EOM pulley locations. Orbit 1.8 computer simulation was performed for each subject by using measured rectus pulley locations. Simulated binocular alignment was compared with the measurements. RESULTS: The maximal SO cross sections of both eyes of each subject were similar, and exhibited similar contractile thickening from supraduction to infraduction. The superior rectus muscle pulleys in three eyes exhibited significant temporal displacement, while the lateral rectus muscle pulleys in five eyes and the medial rectus muscle pulleys in two eyes were displaced significantly inferiorly compared with published norms. Simulations based on observed pulley position abnormalities alone predicted measured Hess screen data better than did simulations incorporating SO weakness, either alone or combined with other structural abnormalities. CONCLUSIONS: Heterotopy of the rectus EOM pulleys may be associated with cyclovertical strabismus that simulates SO palsy.

Displacement of rectus muscle pulleys by torsional muscle surgery for treatment of full macular translocation-induced incyclotropia.

PURPOSE: To elucidate the coronal plane locations of extraocular muscle (EOM) pulleys following torsional muscle surgery. DESIGN: Case report. METHODS: A 76-year-old man underwent advancement of the anterior part of the inferior oblique muscle to treat full macular translocation-induced incyclotropia. Postoperatively, magnetic resonance imaging was used to obtain contiguous, 2-mm-thick coronal orbital images. On each MRI image, the cross-sectional area and center of the EOM was computed, and all rectus EOM positions were translated to the coordinate origin at the area centroid of the globe at the level of pulleys. RESULTS: The superior rectus pulley was displaced temporally, and the lateral rectus pulley was displaced inferiorly more than 2 SD from normal subjects. Coronal plane locations of EOM pulleys of the ipsilateral eye showed extorsion compared with that of the contralesional eye. CONCLUSIONS: Torsional muscle surgery causes an extorsional shift of the superior and lateral rectus pulleys.