High-resolution iris and retinal imaging in multisystemic smooth muscle dysfunction syndrome due to a novel Asn117Lys substitution in ACTA2: a case report.

BACKGROUND: Congenital mydriasis and retinal arteriolar tortuosity are associated with the life-threatening multisystemic smooth muscle dysfunction syndrome (MSMDS) due to mutations in the gene, ACTA2, which encodes alpha-smooth muscle actin (α-SMA). Previous reports attributed MSMDS-related congenital mydriasis to the absence of iris sphincter muscle. Similarly, it has been hypothesized that abnormal proliferation of the vascular smooth muscle cells causes the marked tortuosity of retinal arterioles in MSMDS. In this report, high-resolution ocular imaging reveals unexpected findings that reject previous hypotheses. CASE PRESENTATION: The proband is a 37-year-old female with a history of neonatal patent ductus arteriosus (PDA) ligation, left-sided choreiform movements at the age of 11 and a transient aphasia with right-sided weakness at the age of 30. Her older sister also had PDA ligation and congenital mydriasis but no neurological deficit up to age 41. Magnetic resonance angiogram demonstrated cerebrovascular lesions resembling but distinct from Moyamoya disease, characterised by internal carotid artery dilatation, terminal segment stenosis and absent basal collaterals. Their mother had poorly reactive pupils with asymptomatic cerebral arteriopathy resembling her daughters. All three had prominent retinal arteriolar tortuosity. The daughters were heterozygous and the mother was a somatic mosaic for a novel c.351C > G (p.Asn117Lys) transversion in ACTA2. Iris optical coherence tomography (OCT) showed a hyporeflective band anterior to the pigment epithelium indicating the presence of dysfunctional sphincter muscle. Adaptive optics retinal imaging showed no thickening of the arteriolar vessel wall whilst OCT angiography showed extreme corkscrew course of arterioles suggesting vessel elongation. CONCLUSIONS: In addition to the known association between Met46, Arg179 and Arg258 substitutions and ACTA2-related arteriopathy, this case illustrates the possibility that Asn117 also plays an important role in α-SMA function within the cerebrovascular smooth muscle cell. MSMDS-related congenital mydriasis is due to reduced iris sphincter contractility rather than its absence. Retinal arteriolar tortuosity might be due to longitudinal proliferation of arteriolar smooth muscle cells. The described cerebrovascular and ocular signs are consistent with predicted effects of the novel Asn117Lys substitution in ACTA2.

Intraorbital Penetrating and Retained Foreign Bodies - A Neurosurgical Case Series.

AIM: To present the particularities of the intraorbital foreign bodies from a neurosurgical perspective by summarizing the findings of a case series. MATERIAL AND METHODS: A retrospective study was conducted including a consecutive series of 30 patients with intraorbital foreign bodies treated between 1999 and 2017. Statistical analysis was performed in order to characterize the factors that influence the location of the foreign bodies and the clinical signs. RESULTS: The orbital trauma occurred mostly in working accidents. Multiple intraorbital foreign bodies were found in 23.3% of the patients. Metallic foreign bodies were seen in 66.6%, and 30% had wooden foreign bodies. Nonmetallic foreign bodies were significantly associated with displacement of the eyeball, palpebral oedema and upper lid ptosis. Posterior orbit location was associated with displacement of the eyeball and conjunctival hemorrhage. Intraconal location was associated with mydriasis and conjunctival hemorrhage. The posterior orbit was occupied by foreign bodies in 63% of the patients. The foreign bodies were in the extraconal compartment in 55.55% of the cases. Small foreign bodies tend to be retained in the anterior orbit while large ones tend to be retained in the posterior orbit. CONCLUSION: The diagnosis and management of intraorbital foreign bodies must be tailored according to their type and location and to the clinical aspect of the patient.

Polarization-sensitive optical coherence tomography imaging of the anterior mouse eye.

Polarization-sensitive optical coherence tomography (PS-OCT) enables noninvasive, high-resolution imaging of tissue polarization properties. In the anterior segments of human eyes, PS-OCT allows the visualization of birefringent and depolarizing structures. We present the use of PS-OCT for imaging the murine anterior eye. Using a spectral domain PS-OCT setup operating in the 840-nm regime, we performed in vivo volumetric imaging in anesthetized C57BL/6 mice. The polarization properties of murine anterior eye structures largely replicated those known from human PS-OCT imagery, suggesting that the mouse eye may also serve as a model system under polarization contrast. However, dissimilarities were found in the depolarizing structure of the iris which, as we confirmed in postmortem histological sections, were caused by anatomical differences between both species. In addition to the imaging of tissues in the anterior chamber and the iridocorneal angle, we demonstrate longitudinal PS-OCT imaging of the murine anterior segment during mydriasis as well as birefringence imaging of corneal pathology in an aged mouse.

Síndrome de la transiluminación iridiana aguda bilateral. A propósito de un caso clínico / Bilateral acute iris transillumination syndrome. A case report

OBJETIVO: Presentar el caso clínico de una paciente con el síndrome de la transiluminación iridiana aguda bilateral (BAIT). MÉTODOS: El síndrome de BAIT es una nueva entidad clínica caracterizada por una transiluminación iridiana, dispersión de pigmento en la cámara anterior y una pupila en midriasis media que no responde o es poco sensible a la luz debido a una parálisis del esfínter. Los pacientes con BAIT suelen presentar dolor ocular agudo, fotofobia y ojo rojo. DISCUSIÓN: Presentamos el caso clínico de una mujer de 53 años que, tras ser tratada de una infección del tracto respiratorio superior con moxifloxacino, desarrolló un síndrome de BAIT, diagnosticado en primera instancia de uveítis anterior aguda. CONCLUSIÓN: Este es, hasta donde se conoce, el primer caso reportado en Navarra, aunque es necesaria mayor casuística para establecer patrones claros acerca de esta enfermedad

OBJECTIVE: To present a case report of a patient with a bilateral acute iris transillumination syndrome (BAIT). METHODS: BAIT syndrome is a new clinical condition characterised by severe transillumination of the iris, acute onset of pigment dispersion in the anterior chamber, and a medial mydriatic pupil that is unresponsive or poorly responsive to light, due to a sphincter paralysis. Patients with BAIT generally present with acute ocular pain, photophobia, and red eyes. DISCUSSION: The case is presented of a 53 year-old woman, who, after being treated with moxifloxacin for an upper respiratory tract infection, developed a BAIT syndrome, which was initially diagnosed as acute anterior uveitis. CONCLUSION: As far as is known this is the first case reported in Navarra, but more case reports are needed to establish clear patterns about this condition

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.

PURPOSE: Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management. METHODS: Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed. RESULTS: All patients had congenital mydriasis and related pupillary abnormalities at birth and presented in infancy with a patent ductus arteriosus or aortopulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary, or stroke complications, or unknown causes. CONCLUSION: Based on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications.

New Mydriasis-Free Electroretinogram Recorded with Skin Electrodes in Healthy Subjects.

PURPOSE: To evaluate the reproducibility and consistency of the new mydriasis-free electroretinogram (ERG) with a skin electrode (RETeval) device, to determine the normative values of parameters, and to clarify the usefulness of pupil records to colored-light stimulus. METHODS: A total of 100 eyes of 50 healthy subjects (mean age, 21.4 years) were enrolled. The diagnostic parameters obtained by the RETeval device were examined under the following conditions. The reproducibility was determined with the coefficient of variation (CV). The consistency was examined by intraclass correlation coefficients (ICCs). The mean value and the normal range were analyzed with a 95% confidence interval as the normative values of parameters. The correlation of parameters to pupil records (area ratio, constriction ratio) and flicker ERG was also examined in the diabetic retinopathy assessment protocol. RESULTS: From the CV for each of the two measurements, the amplitude has a low reproducibility compared with the implicit time. Generally good consistency was obtained with both ERG parameters (ICCs = 0.48-0.92). Moderate correlations were found for the white-, red-, and blue-light stimulus in the area ratio and the constriction ratio, respectively (r = 0.44-0.62; P = 0.010-<0.0001). No correlation was observed between pupil and flicker parameters (r = 0.06-0.34; P = 0.646-0.051). CONCLUSIONS: The RETeval device was suggested as a possible screening device to detect the visual afferent diseases by evaluating in combination with the ERG recording and the colored-light pupil response.

Ipsilateral Pupillary Dilation Following Carotid Endarterectomy: A Temporary and Benign Phenomenon.

BACKGROUND AND IMPORTANCE: Cases of post carotid endarterectomy (CEA) Horner's syndrome have been reported, with symptoms attributed to manipulation of the sympathetic plexus situated along the carotid artery; however, these patients presented with the typical constricted pupil. We report the first 3 cases to our knowledge of mydriasis following CEA. CLINICAL PRESENTATION: We present 3 cases of CEA followed by immediate postoperative development of ipsilateral mydriasis. The patients were otherwise at their neurologic baseline and the mydriasis resolved over the ensuing few days. CONCLUSION: We suggest that these cases are secondary to an ischemic phenomenon, specifically to parasympathetic structures such as the ciliary ganglion and/or oculomotor nerve, resulting in autonomic dysfunction manifested by pupillary dilation. A similar finding of mydriasis occurring subsequent to other carotid pathology has been reported, with ischemia to parasympathetic structures also proposed as the underlying etiology. Although pupillary dilation often represents a worrisome neurosurgical sign indicating herniation, it should be recognized that after CEA this finding may be a transient, benign occurrence.

Two patients with the heterozygous R189H mutation in ACTA2 and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome.

De novo heterozygous mutations changing R179 to histidine, leucine, or cysteine in the ACTA2 gene are associated with Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS). Characteristic hallmarks of this condition, caused only by these specific ACTA2 mutations, are congenital mydriasis (mid-dilated, non-reactive pupils), a large persistent ductus arteriosus (PDA), aortic aneurysms evolving during childhood, and cerebrovascular anomalies. We describe two patients, a 3-day-old newborn and a 26-year-old woman, with this unique mutation in association with a huge PDA and an aorto-pulmonary window. In addition, one showed a coarctation of the aortic arch and the other a complete interruption of the aortic arch type A; thereby expanding the spectrum of cardiac congenital heart defect of this syndrome. Each patient displayed a huge PDA and an extra-cardiovascular phenotype consistent with MSMDS. These observations exemplify that a functional alpha 2 smooth muscle actin is necessary for proper cardiovascular organ development, and demonstrate that a very exceptional congenital heart defect (aortopulmonary window) can be caused by a mutation in a gene encoding a contractile protein of vascular smooth muscle cells. © 2017 Wiley Periodicals, Inc.

[Severe Eyeball and Facial Skeletal Injuries Caused by Firefighting Sport]. / Schwerwiegende Augen- und Gesichtsskelettverletzungen beim Feuerwehrsport.

The aim of this work is to draw attention to possible injuries of the eye and the facial skeleton caused by firefighting sport. There was a group of 9 patients presented who were treated from 2006 to 2015 in the Department of Ophthalmology at the University Hospital in Pilsen and diagnosed with severe eyeball contusion after being hit by a jet of water and/or a water pipe. Three cases are presented in detail.

Mydriasis revealing vascular and osteodural compression of the oculomotor nerve: An observational study on five cases.

PURPOSE: To describe a form of neurovascular compression of the third cranial nerve (CNIII) in idiopathic mydriasis, in which a neurovascular "conflict" exists between the oculomotor nerve, the posterior communicating artery and the clinoid process, using high-resolution magnetic resonance imaging (MRI) with fast imaging employing steady acquisition (FIESTA) sequences. METHODS: An 18-month prospective, observational and monocentric case series report was performed. MRI was performed on 5 consecutive patients with idiopathic, unilateral, persistent and nonreactive mydriasis (pure intrinsic palsy of the CNIII). Patients with diplopia, ptosis or ophthalmoplegia were excluded. Cerebral MRI focused on the CNIII pathway from the mesencephalon to the cavernous sinus entry, particularly on the cisternal segment: image acquisition was performed on a 3 Tesla MRI; the protocol included fast imaging employing steady acquisition (FIESTA) and three-dimension time of flight (3D TOF) sequences. RESULTS: All patients presented a neurovascular compression point, involving the CNIII clamped between a tortuous posterior communicating artery (PCoA) and the posterior clinoid process at the entrance of the cavernous sinus. No cases occurred in the root entry zone. There was no compression on the contralateral side. No tumors or aneurysms were found. Thus, the mydriasis was caused by CNIII compression. CONCLUSION: MRI, including FIESTA sequences, revealed a new type of neurovascular conflict between the CNIII, PCoA and posterior clinoid process in patients with incomplete oculomotor palsy. Non-aneurysmal CNIII compression should be considered as a differential diagnosis in the work-up of idiopathic mydriasis. The role of MRI in the work-up of anisocoria should be considered.

Transdermal hyoscine induced unilateral mydriasis.

The authors present a case of unilateral mydriasis in a teenager prescribed transdermal hyoscine hydrobromide (scopolamine) for chemotherapy induced nausea and vomiting. The authors discuss the ocular side-effects associated with this particular drug and delivery system and the potential use of transdermal hyoscine as an antiemetic agent in this group.

Pre-hospital transcranial Doppler in severe traumatic brain injury: a pilot study.

BACKGROUND: Investigation of the feasibility and usefulness of pre-hospital transcranial Doppler (TCD) to guide early goal-directed therapy following severe traumatic brain injury (TBI). METHODS: Prospective, observational study of 18 severe TBI patients during pre-hospital medical care. TCD was performed to estimate cerebral perfusion in the field and upon arrival at the Level 1 trauma centre. Specific therapy (mannitol, noradrenaline) aimed at improving cerebral perfusion was initiated if the initial TCD was abnormal (defined by a pulsatility index >1.4 and low diastolic velocity). RESULTS: Nine patients had a normal initial TCD and nine an abnormal one, without a significant difference between groups in terms of the Glasgow Coma Scale or the mean arterial pressure. Among patients with an abnormal TCD, four presented with an initial areactive bilateral mydriasis. Therapy normalized TCD in five patients, with reversal of the initial mydriasis in two cases. Among these five patients for whom TCD was corrected, only two died within the first 48 h. All four patients for whom the TCD could not be corrected during transport died within 48 h. Only patients with an initial abnormal TCD required emergent neurosurgery (3/9). Mortality at 48 h was significantly higher for patients with an initial abnormal TCD. CONCLUSIONS: Our preliminary study suggests that TCD could be used in pre-hospital care to detect patients whose cerebral perfusion may be impaired.

Mydriasis in association with MMIHS in a female infant: evidence for involvement of the neuronal nicotinic acetylcholine receptor.

We report a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), occurring in association with mydriasis, in a female infant born to consanguineous Asian parents. This association has not previously been reported and is of interest because mydriasis has been found in a murine MMIHS model produced by knockout of the genes coding for the alpha3 subunit or the beta2 and beta4 subunits of the neuronal nicotinic acetylcholine receptor. This may provide an important clue to the genetic basis of MMIHS in humans.

Unilateral mydriasis without ophthalmoplegia--a sign of neurovascular compression? Case report.

OBJECTIVE: We aimed to demonstrate the use of neuroimaging studies in vascular compression of the oculomotor nerve. CLINICAL PRESENTATION: A 24-year-old woman was noted by her dentist to have anisocoria, with the left pupil being larger than the right. After detailed ophthalmologic and neurological examination, we proceeded to perform neuroimaging. T2-weighted images (2 mm) and constructive interference in steady-state (0.3 mm) images were utilized. INTERVENTION: Magnetic resonance imaging showed that duplicated left superior cerebellar artery, a prominent posterior communicating artery, and a posterior cerebral artery combined to compress the superomedial portion of the left oculomotor nerve. CONCLUSION: With continued improvements in neuroimaging, we think that more cases of isolated cranial neuropathies previously labeled as "idiopathic" will be shown to result from vascular compression.