Increased Orbital Muscle Fraction Diagnosed by Semi-Automatic Volumetry: A Risk Factor for Severe Visual Impairment with Excellent Response to Surgical Decompression in Graves' Orbitopathy.

Graves' orbitopathy (GO) leads to increased orbital tissue and causes symptoms such as exophthalmos, functional complaints, or dysthyroid optic neuropathy. Different GO types with fat and/or muscle enlargement were identified, and increased muscle appears to particularly influence visual status and treatment response. The current study examines visual parameters dependent on orbital muscle volume fraction in a surgically treated GO cohort. After volumetric analysis of the preoperative orbital content, 83 orbits in 47 patients were categorized into predefined groups (increased or not-increased muscle fraction). All cases underwent pterional orbital decompression, and pre- and postoperative visual status was retrospectively analyzed. Forty-one orbits revealed increased and 42 orbits revealed not-increased muscle volume (mean fraction 29.63% versus (vs.) 15.60%). The preoperative visual acuity (VA) was significantly lower in orbits with increased vs. not-increased muscle volume (mean VA 0.30 vs. 0.53, difference 2.5 lines). After surgery, mean VA improved significantly by 1.7 lines in orbits with increased muscle volume. Not preoperative, but postoperative exophthalmos was significantly lower in orbits with not-increased muscle volume. Increased orbital muscle is associated with significantly reduced VA, but can be remarkably improved by pterional orbital decompression. Therefore, surgical therapy should be considered particularly in decreased VA with orbital muscle enlargement.

Pterional Orbit Decompression in Grave Disease with Dysthyroid Optic Neuropathy.

OBJECTIVE: The choice of surgical technique in sight-threatening Grave orbitopathy remains controversial. Available data are mostly derived from mixed cohorts with multiple surgical indications and techniques. The authors assessed predictors for visual outcome after standardized pterional orbital decompression for dysthyroid optic neuropathy. METHODS: Retrospective analysis of 62 pterional orbital decompressions performed on 40 patients with dysthyroid optic neuropathy. RESULTS: Visual acuity improved by an average of 3.8 lines in eyes with preoperative visual impairment (95% confidence interval [CI]: 1.8-5.8 lines, P < 0.001) and remained stable in eyes without prior visual impairment (95% CI -1.3 to 1 line, P = 0.81). Proptosis was reduced by an average of 3.1 mm (95% CI 1.8-4.3 mm, P < 0.001). Higher degrees of proptosis were predictive of worse visual outcomes (P = 0.017). New-onset diplopia developed in 2 patients, while previous diplopia resolved after surgery in 6 patients. CONCLUSIONS: This cohort is the largest series of pterional orbit decompressions and the first to focus exclusively on dysthyroid neuropathy. Complication rates were low. Decompression surgery was highly effective at restoring and maintaining visual acuity in patients with dysthyroid optic neuropathy.

EpCAM controls morphogenetic programs during zebrafish pronephros development.

Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is dynamically expressed in human and murine renal epithelia during development. The levels of EpCAM in the renal epithelium are upregulated both during regeneration after ischemia/reperfusion injury and in renal-derived carcinomas. The role of EpCAM in early kidney development, however, has remained unclear. The zebrafish pronephros shows a similar segmentation pattern to the mammalian metanephric nephron, and has recently emerged as a tractable model to study the regulatory programs governing early nephrogenesis. Since EpCAM shows persistent expression in the pronephros throughout early development, we developed a method to study the global changes in gene expression in specific pronephric segments of wild type and EpCAM-deficient zebrafish embryos. In epcam mutants, we found 379 differentially expressed genes. Gene ontology analysis revealed that EpCAM controls various developmental programs, including uretric bud development, morphogenesis of branching epithelium, regulation of cell differentiation and cilium morphogenesis.

The polarity protein Inturned links NPHP4 to Daam1 to control the subapical actin network in multiciliated cells.

Motile cilia polarization requires intracellular anchorage to the cytoskeleton; however, the molecular machinery that supports this process remains elusive. We report that Inturned plays a central role in coordinating the interaction between cilia-associated proteins and actin-nucleation factors. We observed that knockdown of nphp4 in multiciliated cells of the Xenopus laevis epidermis compromised ciliogenesis and directional fluid flow. Depletion of nphp4 disrupted the subapical actin layer. Comparison to the structural defects caused by inturned depletion revealed striking similarities. Furthermore, coimmunoprecipitation assays demonstrated that the two proteins interact with each other and that Inturned mediates the formation of ternary protein complexes between NPHP4 and DAAM1. Knockdown of daam1, but not formin-2, resulted in similar disruption of the subapical actin web, whereas nphp4 depletion prevented the association of Inturned with the basal bodies. Thus, Inturned appears to function as an adaptor protein that couples cilia-associated molecules to actin-modifying proteins to rearrange the local actin cytoskeleton.