Challenging presentations of cavernous sinus thrombophlebitis

AIM: The purpose of this study was to describe two challenging cases of septic cavernous sinus thrombosis (CST), which presented with vastly different clinical signs and symptoms. METHODS: We present two cases of CST with markedly differing clinical presentations, medical comorbidities, and degree of impairment. Initial imaging of each patient failed to show thromboembolic disease. RESULTS: Both patients required multiple imaging procedures to arrive at the correct diagnosis. Each child did respond to treatment once the correct diagnosis was made. CONCLUSION: CST can have a highly variable clinical presentation, from a subtle sixth nerve palsy to complete ophthalmoplegia and loss of periorbital sensation and corneal reflex. Onset of symptoms may be acute and fulminant or indolent and delayed. The diagnosis is challenging, requiring clinical suspicion and confirmation by imaging. These cases illustrate the importance of retaining clinical suspicion when cranial nerve palsies persist and how valuable rescanning a patient can be

Use of Biologic Agents in Ocular Manifestations of Rheumatic Disease

Biologic agents have dramatically shifted the treatment paradigm for rheumatic disease. Use of these agents can decrease disease burden, allow the patient to be weaned from corticosteroids, and reduce the likelihood of relapse. Eye disease associated with rheumatic conditions may present with a wide range of signs and symptoms. This coexisting pathology should not be overlooked and should be considered a reason for initiation or continuation of biologic therapy. Additionally, many of the ocular manifestations of rheumatic disease respond preferentially to specific targeting molecules. This paper summarizes the available studies on the use, efficacy, and safety of biologic agents in the treatment of ocular manifestations of rheumatic disease

New advances in amblyopia therapy II: refractive therapies

The treatment of anisometropic or ametropic amblyopia has traditionally enjoyed a high treatment success rate. Early initiation and consistent use of spectacle correction can completely resolve amblyopia in a majority of patients. For those with anisometropic amblyopia that fail to improve with glasses wear alone, patching or atropine penalisation can lead to equalisation of visual acuity. However, successful treatment requires full-time compliance with refractive correction and this can be a challenge for a patient population that often has one eye with good acuity without correction. Other barriers for a select population with high anisometropic or ametropic amblyopia include rejection of glasses for various reasons including discomfort, behavioural or sensory problems, postural issues and visually significant aniseikonia. When consistent wear of optical correction proves difficult and patching/atropine remains a major obstacle, surgical correction of refractive error has proven success in achieving vision improvement. Acting as a means to achieve spectacle independence or reducing the overall needed refractive correction, refractive surgery can offer a unique treatment option for this patient population. Laser surgery, phakic intraocular lenses and clear lens exchange are three approaches to altering the refractive state of the eye. Each has documented success in improving vision, particularly in populations where glasses wear has not been possible. Surgical correction of refractive error has a risk profile greater than that of more traditional therapies. However, its use in a specific population offers the opportunity for improving visual acuity in children who otherwise have poor outcomes with glasses and patching/atropine alone

Exome sequencing identifies novel and recurrent mutations in GJA8 and CRYGD associated with inherited cataract

BACKGROUND: Inherited cataract is a clinically important and genetically heterogeneous cause of visual impairment. Typically, it presents at an early age with or without other ocular/systemic signs and lacks clear phenotype-genotype correlation rendering both clinical classification and molecular diagnosis challenging. Here we have utilized trio-based whole exome sequencing to discover mutations in candidate genes underlying autosomal dominant cataract segregating in three nuclear families. RESULTS: In family A, we identified a recurrent heterozygous mutation in exon-2 of the gene encoding γD-crystallin (CRYGD; c.70C > A, p.Pro24Thr) that co-segregated with ‘coralliform’ lens opacities. Families B and C were found to harbor different novel variants in exon-2 of the gene coding for gap-junction protein α8 (GJA8; c.20T > C, p.Leu7Pro and c.293A > C, p.His98Pro). Each novel variant co-segregated with disease and was predicted in silico to have damaging effects on protein function. CONCLUSIONS: Exome sequencing facilitates concurrent mutation-profiling of the burgeoning list of candidate genes for inherited cataract, and the results can provide enhanced clinical diagnosis and genetic counseling for affected families. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40246-014-0019-6) contains supplementary material, which is available to authorized users

Spontaneous activity promotes synapse formation in a cell-type-dependent manner in the developing retina

Spontaneous activity is thought to regulate synaptogenesis in many parts of the developing nervous system. In vivo evidence for this regulation, however, is scarce and comes almost exclusively from experiments in which normal activity was reduced or blocked completely. Thus, whether spontaneous activity itself promotes synaptogenesis or plays a purely permissive role, remains uncertain. In addition, how activity influences synapse dynamics to shape connectivity and whether its effects among neurons are uniform or cell type-dependent is unclear. In mice lacking the cone-rod homeobox gene (Crx), photoreceptors (PRs) fail to establish normal connections with bipolar cells (BCs). Here, we find that retinal ganglion cells (RGCs) in Crx−/− mice become rhythmically hyperactive around the time of eye-opening; as a result of increased spontaneous glutamate release from BCs. This elevated neurotransmission enhances synaptogenesis between BCs and RGCs, without altering the overall circuit architecture. Using live imaging, we discover that spontaneous activity selectively regulates the rate of synapse formation, not elimination, in this circuit. Reconstructions of the connectivity patterns of three BC types with a shared RGC target further revealed that neurotransmission specifically promotes the formation of multisynaptic appositions from one BC type without affecting the maintenance or elimination of connections from the other two. While hyperactivity in Crx−/− mice persists, synapse numbers do not increase beyond four weeks of age, suggesting closure of a critical period for synaptic refinement in the inner retina. Interestingly, despite their hyperactivity, RGC axons maintain normal eye-specific territories and cell type-specific layers in the dorsolateral geniculate nucleus (dLGN)

An allosteric regulator of R7-RGS proteins influences light-evoked activity and glutamatergic waves in the inner retina

In the outer retina, G protein-coupled receptor (GPCR) signaling mediates phototransduction and synaptic transmission between photoreceptors and ON bipolar cells. In contrast, the functions of modulatory GPCR signaling networks in the inner retina are less well understood. We addressed this question by determining the consequences of augmenting modulatory Gi/o signaling driven by endogenous transmitters. This was done by analyzing the effects of genetically ablating the R7 RGS-binding protein (R7BP), a membrane-targeting protein and positive allosteric modulator of R7-RGS (regulator of the G protein signaling 7) family that deactivates Gi/oα subunits. We found that R7BP is expressed highly in starburst amacrine cells and retinal ganglion cells (RGCs). As indicated by electroretinography and multielectrode array recordings of adult retina, ablation of R7BP preserved outer retina function, but altered the firing rate and latency of ON RGCs driven by rods and cones but not rods alone. In developing retina, R7BP ablation increased the burst duration of glutamatergic waves whereas cholinergic waves were unaffected. This effect on glutamatergic waves did not result in impaired segregation of RGC projections to eye-specific domains of the dorsal lateral geniculate nucleus. R7BP knockout mice exhibited normal spatial contrast sensitivity and visual acuity as assessed by optomotor reflexes. Taken together these findings indicate that R7BP-dependent regulation of R7-RGS proteins shapes specific aspects of light-evoked and spontaneous activity of RGCs in mature and developing retina