Faculty Bibliography

PURPOSE: To evaluate the efficacy of bilateral posterior superior oblique tenectomy for the treatment of A-pattern strabismus due to superior oblique overaction regardless of the magnitude of the pattern. METHODS: The medical records of patients with A-pattern esotropia or exotropia in the presence of superior oblique overaction who underwent combined horizontal muscle surgery along with bilateral superior oblique posterior 7/8 tenectomy from 2003 to 2013 were retrospectively reviewed. Patients with at least 3 months' follow-up were included. RESULTS: A total of 73 patients were included. Of these, 46 had esotropia; 27, exotropia. The preoperative A-pattern deviation for the study population was 19.6Delta +/- 11.4Delta (range, 10-60), with a final postoperative patten collapse of 18.2 +/- 3.6. Superior oblique overaction was 2.3 +/- 0.7 preoperatively and 0.3 +/- 0.7 postoperatively. Overall, 87.7% of patients had a successful collapse of their pattern to <10Delta following the initial bilateral superior oblique posterior tenectomy, with an additional 4.1% following a second procedure. Of patients with a pattern deviation of <25Delta, 87.9% had successful collapse of the pattern following 1 surgery, and 86.7% of patients who had a pattern of >/=25Delta had successful collapse. Postoperatively, 7 patients demonstrated mild inferior oblique overaction. No surgical complications were noted. CONCLUSIONS: A uniform dose of bilateral posterior 7/8 tenectomy surgery successfully collapses A-pattern deviations of all magnitudes.

PURPOSE OF REVIEW: This review summarizes current patterns in the use of immunosuppressive agents in patients with uveitis. RECENT FINDINGS: A number of immunosuppressive agents are currently available for the treatment of uveitis. Reports of safety and efficacy, although numerous, have been largely nonrandomized and performed without controls, limiting, to some extent, the strength and generalizability of their conclusions. Nonetheless, the volume of case reports and case series provides compelling evidence that immunosuppressive agents are effective at providing long-term control in patients with moderate to severe chronic or recurrent uveitis. The choice of immunosuppressive agent is complex, and depends on the cause and severity of the patient's underlying inflammation, the presence or absence of associated systemic inflammation, and the patient's prior response to immunosuppressive treatments. SUMMARY: Although corticosteroids remain the primary initial treatment for patients with uveitis, use of noncorticosteroid immunosuppressive agents in selected patients with uveitis allows for improved control and decreased risk of corticosteroid-induced side effects

Voltage-dependent sodium (Na(+)) channels are highly concentrated at nodes of Ranvier in myelinated axons and play a key role in promoting rapid and efficient conduction of action potentials by saltatory conduction. The molecular mechanisms that direct their localization to the node are not well understood but are believed to involve contact-dependent signals from myelinating Schwann cells and interactions of Na(+) channels with the cytoskeletal protein, ankyrin G. Two cell adhesion molecules (CAMs) expressed at the axon surface, Nr-CAM and neurofascin, are also linked to ankyrin G and accumulate at early stages of node formation, suggesting that they mediate contact-dependent Schwann cell signals to initiate node development. To examine the potential role of Nr-CAM in this process, we treated myelinating cocultures of DRG (dorsal root ganglion) neurons and Schwann cells with an Nr-CAM-Fc (Nr-Fc) fusion protein. Nr-Fc had no effect on initial axon-Schwann cell interactions, including Schwann cell proliferation, or on the extent of myelination, but it strikingly and specifically inhibited Na(+) channel and ankyrin G accumulation at the node. Nr-Fc bound directly to neurons and clustered and coprecipitated neurofascin expressed on axons. These results provide the first evidence that neurofascin plays a major role in the formation of nodes, possibly via interactions with Nr-CAM

The structurally related cell adhesion molecules L1 and Nr-CAM have overlapping expression patterns in cerebellar granule cells. Here we analyzed their involvement in granule cell development using mutant mice. Nr-CAM-deficient cerebellar granule cells failed to extend neurites in vitro on contactin, a known ligand for Nr-CAM expressed in the cerebellum, confirming that these mice are functionally null for Nr-CAM. In vivo, Nr-CAM-null cerebella did not exhibit obvious histological defects, although a mild size reduction of several lobes was observed, most notably lobes IV and V in the vermis. Mice deficient for both L1 and Nr-CAM exhibited severe cerebellar folial defects and a reduction in the thickness of the inner granule cell layer. Additionally, anti-L1 antibodies specifically disrupted survival and maintenance of Nr-CAM-deficient granule cells in cerebellar cultures treated with antibodies. The combined results indicate that Nr-CAM and L1 play a role in cerebellar granule cell development, and suggest that closely related molecules in the L1 family have overlapping functions

Nr-CAM is a member of the L1 subfamily of cell adhesion molecules (CAMs) that belong to the immunoglobulin superfamily. To explore the role of Nr-CAM in the developing nervous system, we prepared specific antibodies against both chick and mouse Nr-CAM using recombinant Fc fusion proteins of chick Nr-CAM and mouse Nr-CAM, respectively. First, we show the specificity of the new anti-chick Nr-CAM antibody compared with a previously employed antibody using the expression patterns of Nr-CAM in the chick spinal cord and floor plate and on commissural axons, where Nr-CAM has been implicated in axon guidance. Using the anti-mouse Nr-CAM antibody, we then studied the expression patterns of Nr-CAM in the developing mouse nervous system along with the patterns of two related CAMs, L1, which labels most growing axons, and TAG-1, which binds to Nr-CAM and has a more restricted distribution. Major sites that are positive for Nr-CAM are specialized glial formations in the ventral midline, including the floor plate in the spinal cord, the hindbrain and midbrain, the optic chiasm, and the median eminence in the forebrain. Similar to what is seen in the chick spinal cord, Nr-CAM is expressed on crossing fibers as they course through these areas. In addition, Nr-CAM is found in crossing fiber pathways, including the anterior commissure, corpus callosum, and posterior commissure, and in nondecussating pathways, such as the lateral olfactory tract and the habenulointerpeduncular tract. Nr-CAM, for the most part, is colocalized with TAG-1 in all of these systems. Based on in vitro studies indicating that the Nr-CAM-axonin-1/TAG-1 interaction is involved in peripheral axonal growth and guidance in the spinal cord [Lustig et al. (1999) Dev Biol 209:340-351; Fitzli et al. (2000) J Cell Biol 149:951-968], the expression patterns described herein implicate a role for this interaction in central nervous system axon growth and guidance, especially at points of decussation. Nr-CAM also is expressed in cortical regions, such as the olfactory bulb. In the hippocampus, however, TAG-1-positive areas are segregated from Nr-CAM-positive areas, suggesting that, in neuropilar regions, Nr-CAM interacts with molecules other than TAG-1.

Specialized paranodal junctions form between the axon and the closely apposed paranodal loops of myelinating glia. They are interposed between sodium channels at the nodes of Ranvier and potassium channels in the juxtaparanodal regions; their precise function and molecular composition have been elusive. We previously reported that Caspr (contactin-associated protein) is a major axonal constituent of these junctions (Einheber et al., 1997). We now report that contactin colocalizes and forms a cis complex with Caspr in the paranodes and juxtamesaxon. These proteins coextract and coprecipitate from neurons, myelinating cultures, and myelin preparations enriched in junctional markers; they fractionate on sucrose gradients as a high-molecular-weight complex, suggesting that other proteins may also be associated with this complex. Neurons express two contactin isoforms that differ in their extent of glycosylation: a lower-molecular-weight phosphatidylinositol phospholipase C (PI-PLC)-resistant form is associated specifically with Caspr in the paranodes, whereas a higher-molecular-weight form of contactin, not associated with Caspr, is present in central nodes of Ranvier. These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr. Treatment of myelinating cocultures of Schwann cells and neurons with RPTPbeta-Fc, a soluble construct containing the carbonic anhydrase domain of the receptor protein tyrosine phosphatase beta (RPTPbeta), a potential glial receptor for contactin, blocks the localization of the Caspr/contactin complex to the paranodes. These results strongly suggest that a preformed complex of Caspr and contactin is targeted to the paranodal junctions via extracellular interactions with myelinating glia