Optic disc edema as a possible complication of Imatinib mesylate (Gleevec)

BACKGROUND: Imatinib is effective for a variety of hematologic and nonhematologic malignancies. Well-known ocular side effects are periorbital edema, epiphora, extraocular muscle palsy, and blepharoconjunctivitis. However, optic disc edema has not been reported as a complication of imatinib mesylate. Herein, we describe a patient with chronic myeloid leukemia (CML) who developed optic disc edema during treatment with imatinib. CASE: A 14-year-old Korean girl was referred to ophthalmology for a 3-week history of photopsia in both eyes. She had started taking imatinib daily 2 months previously for CML. At the initial exam, slit lamp showed optic disc edema in both eyes, even though visual acuity was 20/20 and other optic nerve function evaluations were within normal limits. We recommended to the oncologist discontinuation of the imatinib treatment. OBSERVATIONS: When the patient was followed for 1 week after stopping imatinib treatment, the frequency of photopsia decreased and the optic disc edema improved. Because a second examination 3 weeks after discontinuation of imatinib revealed much improved optic disc edema, she restarted the imatinib treatment. No ocular side effects have been noted so far. CONCLUSIONS: Optic disc edema should be considered one of the complications associated with imatinib. We propose discontinuation of the treatment for a short period when optic disc edema occurs.     

【In Press】Effect of two different doses of intravitreal bevacizumab with temporal retina-sparing laser photocoagulation for retinopathy of prematurity

This study aims to compare the efficacy and safety between two different doses of intravitreal bevacizumab injection (IVB) with temporal retina-sparing laser photocoagulation (TRSL) for retinopathy of prematurity (ROP). We retrospectively evaluated 22 eyes of ROP infants who underwent IVB combined with partial TRSL for stage 3+ zone I or posterior zone II ROP. Laser photocoagulation was applied on the avascular retina, sparing two-disc-diameter width temporal avascular area anterior to ridge. A half dose (0.625 mg) or minimal dose (0.25 mg) of IVB was conducted. Four eyes in minimal dose group were retreated with IVB and laser photocoagulation on the spared retina. Of those 4 retreated eyes, three developed preretinal hemorrhage around the ridge after the first treatment, resulting in fibrotic macular dragging. A half dose of IVB may be more effective than a minimal dose with partial TRSL for ROP. Preretinal hemorrhage may be a harbinger of poor prognosis.     

Impact of blinking on ocular surface and tear film parameters

Purpose

To investigate the influence of blinking on tear film parameters, ocular surface characteristics, and dry eye symptomology.

Primary ovarian pregnancy two years after bilateral tubal ligation. A case report

This is the first documented case of intrafollicular ovarian pregnancy following bilateral tubal ligation. The patency of the previously ligated tube was demonstrated by hysterosalpinography. It appears that the incidence of ovarian pregnancy is not related to the rising incidence of tubal pregnancy.     

Effect of Muscle Relaxants on Short-term Results of Exotropia Surgery: A Focus on Resection Procedures

Purpose

We investigated the effect of muscle relaxants (atracurium) on the outcomes of intermittent exotropia surgery under general anesthesia, with a focus on resection procedures.

Methods

Thirty four patients who underwent recession and resection (R&R) were divided into two groups: atracurium usage (group A, n=18) and no atracurium usage (group B, n=16). Patients were divided into two subgroups according to the amount of resection of the medial rectus (MR): less than 5 mm (group 1, n=13) or 5 mm and greater (group 2, n=21). Deviation angles were compared between groups and subgroups. Surgical outcome was defined as successful if distant deviation angles were equal to or less than 10 prism diopters.

Results

The overall postoperative deviation angles did not show statistically significant differences between groups A and B. However, in patients with larger MR resections (≥ 5 mm), the 1 week postoperative distant deviation was significantly larger in group A (1.8±2.6 PD) than in group B (-1.6±4.6 PD, p=0.048 by t-test). The overall undercorrection rate at 3 months postoperatively for group A was 16.7%, which was higher than that of group B (6.3%), and the difference was even larger in subgroups with larger MR resections (≥ 5 mm): 18.2% in group A and 0% in group B.

Conclusions

Patients who underwent R&R procedures under general anesthesia with a muscle relaxant tended to be less corrected than those without muscle relaxant, especially in the early postoperative period and with a larger MR resection equal to or greater than 5 mm. However, there was no significant difference in the later postoperative period.     

SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.     

Tectorigenin, an isoflavone of Pueraria thunbergiana Benth., induces differentiation and apoptosis in human promyelocytic leukemia HL-60 cells

Cytotoxic effects of six isoflavonoids, tectorigenin, glycitein, tectoridin, glycitin, 6'-O-xylosyltectoridin, and 6'-O-xylosylglycitin isolated from the flower of Pueraria thunbergiana Benth. together with genistein, a known differentiation and apoptosis inducer, were examined. Among these isoflavonoids, tectorigenin and genistein exhibited cytotoxicity against various human cancer cells; glycitein showed only mild cytotoxicity. These results suggest that the isoflavone structure and 5-hydroxyl group are crucial for the cytotoxic properties and that glycosides are inactive. Moreover, tectorigenin induced differentiation of human promyelocytic leukemia HL-60 cells to granulocytes and monocytes/macrophages, and caused apoptotic changes of DNA in the cells, as did genistein. Tectorigenin also inhibited autophosphorylation of epidermal growth factor (EGF) receptor by EGF and decreased the expression of Bcl-2 protein, with less activity than genistein. From these results, tectorigenin may be a possible therapeutic agent for leukemia.     

Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability

To develop a hyaluronic microsphere with the improved oral bioavailability of poorly water-soluble cyclosporin A (CsA), the microspheres were prepared with varying ratios of sodium hyaluronate (HA)/sodium lauryl sulfate (SLS)/CsA using a spray-drying technique. The effects of HA and SLS on the dissolution and solubility of CsA in microspheres were investigated. The CsA-microsphere prepared with HA/SLS/CsA at the ratio of 4/2/1 gave the highest solubility and dissolution rate of CsA among those formulae tested. As solubility and dissolution rate of CsA were increased about 17- and 2-fold compared to CsA powder, respectively, this CsA-microsphere was selected as an optimal formula for oral delivery in rats. The CsA-microsphere and Sandimmun neoral sol gave significantly higher blood levels compared with CsA powder alone. Moreover, the AUC, T(max) and C(max) values of CsA in CsA-microsphere were not significantly different from those in Sandimmun neoral sol in rats, indicating that CsA-microsphere was bioequivalent to the commercial product in rats. Our results demonstrated that the CsA-microsphere prepared with HA and SLS, with improved bioavailability of CsA, might have been useful to deliver a poorly water-soluble CsA.