Corneal Toxicity Associated With Aquarium Coral Palytoxin.

PURPOSE: To report a series of patients who developed corneal toxicity after exposure to aquarium coral palytoxin. DESIGN: Multicenter retrospective case series. METHODS: Retrospective review. RESULTS: Seven patients presented with corneal findings ranging from superficial punctate epitheliopathy to bilateral corneal melt with subsequent perforation. Among those with mild corneal findings, resolution was achieved with topical steroids and lubrication, whereas some patients who developed progressive corneal melt required therapeutic penetrating keratoplasty. The history in all patients revealed exposure to aquarium zoanthid corals shortly before disease onset. A review of the literature revealed that there are few prior reports of coral-associated corneal toxicity and that some species of coral secrete a substance known as palytoxin, a potent vasoconstrictor that inhibits the membranous sodium-potassium ATPase pump across cell types and can cause rapid death if inhaled or ingested. CONCLUSIONS: This is the largest case series to date demonstrating patients with aquarium coral palytoxin-associated corneal toxicity, and is the first to provide details of related histopathologic findings. Similar to other forms of toxic keratoconjunctivitis, a detailed history and careful clinical assessment are required, as well as timely removal of the offending agent from the patients' ocular milieu and environment. Mild ocular surface and corneal disease may be treated effectively with aggressive topical steroid therapy and lubrication. Given the potential severity of ocular as well as systemic adverse effects, there should be increased awareness of this entity among eye care professionals, aquarium enthusiasts, and the general public.

Subjective and Objective Measures in the Treatment of Hemifacial Spasm With OnabotulinumtoxinA.

PURPOSE: To evaluate the Sunnybrook Facial Grading System (SFGS) and Facial Clinimetric Evaluation (FaCE) Scale Instrument outcomes when treating hemifacial spasm (HFS) with onabotulinumtoxinA. METHODS: An Institutional Review Board-approved retrospective review of records of 66 HFS patients treated with onabotulinumtoxinA. SFGS and FaCE surveys were completed prior to onabotulinumtoxinA therapy and at 1 month follow up. Surveys were analyzed for differences using paired Student t tests, with statistical significance set at p < 0.05. Correlations were determined using Spearman correlation (rs), with coefficients of ≥0.40 or ≤-0.40 considered significant. RESULTS: There were 22 complete data sets. SFGS composite score improved from mean, 56.9 (SD, 12.3) to 63.6 (SD, 12.3), p < 0.01. SFGS subdomain synkinesis score significantly improved (p < 0.01). The FaCE scale subdomain oral function significantly worsened (p = 0.05). The Δ pre-/post-SFGS composite score did not correlate with the Δ pre-/post-FaCE composite score (rs = 0.24). There was a significant positive correlation between SFGS composite score and FaCE social function score (rs = 0.462, p = 0.03) and between SFGS voluntary movement score and FaCE social function score (rs = 0.477, p = 0.03). Subgroup analysis of single FaCE questions demonstrated no statistical change in subjective dry eye (p = 0.30). CONCLUSIONS: There was an improvement in social functioning in treated HFS patients, which positively correlated with improvement in overall objective voluntary facial movement. There was no statistical difference in subjective dry eye symptoms. The overall SFGS composite score improved following treatment of HFS with botulinum toxin. This information can be used when counseling expected outcomes in HFS patients treated with onabotulinumtoxinA.

Acute and chronic mu opioids differentially regulate thrombospondins 1 and 2 isoforms in astrocytes.

Chronic opioids induce synaptic plasticity, a major neuronal adaptation. Astrocyte activation in synaptogenesis may play a critical role in opioid tolerance, withdrawal, and dependence. Thrombospondins 1 and 2 (TSP1/2) are astrocyte-secreted matricellular glycoproteins that promote neurite outgrowth as well as dendritic spine and synapse formation, all of which are inhibited by chronic µ opioids. In prior studies, we discovered that the mechanism of TSP1 regulation by µ opioids in astrocytes involves crosstalk between three different classes of receptors, µ opioid receptor, EGFR and TGFßR. Moreover, TGFß1 stimulated TSP1 expression via EGFR and ERK/MAPK activation, indicating that EGFR is a signaling hub for opioid and TGFß1 actions. Using various selective antagonists, and inhibitors, here we compared the mechanisms of chronic opioid regulation of TSP1/2 isoform expression in vivo and in immortalized rat cortical astrocytes. TSP1/2 release from astrocytes was also monitored. Acute and chronic µ opioids, morphine, and the prototypic µ ligand, DAMGO, modulated TSP2 protein levels. TSP2 but not TSP1 protein content was up-regulated by acute (3 h) morphine or DAMGO by an ERK/MAPK dependent mechanism. Paradoxically, TSP2 protein levels were altered neither by TGFß1 nor by astrocytic neurotrophic factors, EGF, CNTF, and BMP4. TSP1/2 immunofluorescence was increased in astrocytes subjected to scratch-wounding, suggesting TSPs may be useful markers for the "reactive" state of these cells and potentially for different types of injury. Previously, we determined that chronic morphine attenuated both neurite outgrowth and synapse formation in cocultures of primary astrocytes and neurons under similar temporal conditions that µ opioids reduced TSP1 protein levels in astrocytes. Here we found that, after the same 8 day treatment, morphine or DAMGO diminished TSP2 protein levels in astrocytes. Therefore, µ opioids may deter synaptogenesis via both TSP1/2 isoforms, but by distinct mechanisms.