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The synthesis of the ABC ring fragment of gymnocin-A is described. The key feature of this approach was the convergent BC ring formation using an oxiranyl anion coupling, which was followed by intramolecular Williamson ether synthesis and the reductive etherification of an α-acetoxy acetal. The five-membered A ring was then constructed on the seven-membered B ring by radical cyclization of a β-alkoxy acrylate derivative.

Purpose : To report the efficacy of intravitreal injections of bevacizumab for diabetic macular edema (DME) in the short-term. Design : Retrospective, noncomparative, interventional case series.Methods : Medical records of 20 eyes of 19 patients who underwent intravitreal injections of bevacizumab for persistent diabetic macular edema were reviewed retrospectively. All eyes received intravitreal injections of bevacizumab (1.25 mg/ 0.05 ml). The clinical course of best-corrected visual acuity (BCVA) using a logarithm of the minimum angle of resolution chart, and averaged foveal retinal thickness using an optical coherence tomography (OCT) were monitored for up to four weeks after the injection. Results : BCVA at one week improved by two lines or more in six eyes (30%) and in nine eyes (45%) at four weeks. However, no significant improvement in the mean BCVA from baseline was observed at one week (P>0.05) and four weeks (P>0.05). Mean retinal thicknesses (RT) were 411±170μm at baseline, 349±102μm at one week after the injection (P0.05). One week after the injection, significant regression of macular edema was seen. However, recurrence occurred at four weeks. No complications such as severe vision loss, endophthalmitis, or systemic events developed. Conclusion : No changes in BCVA and RT were observed in the short-term observation after the intravitreal injection of bevacizumab for DME.

Purpose : To investigate cases with massive subretinal hemorrhage after pho- todynamic therapy(PDT). Subjects and Methods : We studied four cases(3 men and 1 woman, mean 80.5 yeas old) with massive subretinal hemorrhage after PDT about type of disease, spot size, period to the onset of hemorrhage, visual acuity (VA) before and after PDT. Results : Four cases consisted of one with age-related macula degeneration (AMD) and 3 with polypoidal choroidal vasculopathy (PCV). The average spot size of PDT was 5525m. Two patients underwent the second PDT about 3 months after the initial PDT. Four periods to the onset of hemorrhage were 22, 27, 137, and 208 days respectively. The latter 2 cases underwent PDT twice, and the periods were the days from the initial PDT. Two patients among four underwent vitrectomy. Average VA before PDT was 0.20, and the fi- nal one was 0.02 after PDT. Conclusions : PDT has a risk to cause massive subretinal hemorrhage leading to grave visual disturbance. Especially PDT for PCV seems to have more risk. Therefore we need to inform patients about the risk before PDT, since treating patients with massive subreti- nal hemorrhage is very difficult J. Med. Invest. 55 : 231-235, August, 2008

Purpose : To determine whether or not a sub-Tenon's capsule injection of triam- cinolone acetonide(TA) is an effective treatment for refractory diabetic macular edema after vitrectomy. Methods : Thirty-nine eyes of 26 patients with diabetic macular edema were injected with 20 mg TA into the sub-Tenon's capsule. The central macular thickness (CMT) measured by an optical coherence tomography (OCT) and visual acuities were compared between pre-treatment and 1, 3 months post-treatment. Results : The decrease in the mean CMT between the baseline (435 m) and 1month (326 m) or 3months (303 m) time points was statistically significant. Seven eyes (70% at 1 month and 3 months post-treatment in the vitrectomized eyes or PPV(pars plana vitrectomy)(+) group, 15 eyes(52% at 1 month, and 19 eyes (66% at 3 months in the non-vitrectomized eyes or PPV(-)group maintained 20% reduction in CMT from pre-treatment with a single injection of TA. The recurrence of macular edema was observed in 1 eye (14% in the PPV(+)group, and 3 eyes (16% in the PPV(-)group. Conclusion : The sub-Tenon's capsule injection of TA was effective for refractory diabetic macular edema after vitrectomy. In addition, it was suggested that the treatment of vitrectomized eyes was more effective than that of non-vitrectomized eyes. J. Med. Invest. 55 : 279-282, August, 2008

Purpose : To evaluate outcomes of submacular surgery to remove massive submacular hard exudates with diabetic macular edema. Design : Retrospective, noncomparative, interventional consecutive case series. Participants : Fifty-six eyes of 40 patients with massive submacular hard exudates with diabetic macular edema. Intervention : Submacular surgery was performed to remove massive submacular hard exudates. Main Outcome Measures : Preoperative and postoperative visual acuities and clinical findings. All patients were followed for more than 1 year postoperatively. Results : The macular hard exudates underlying the fovea almost disappeared, and macular edema remarkably reduced following surgery. Visual acuities ranged from 0.01 to 0.3 before surgery, and from 0.04 to 1.0 after surgery. Visual acuity improved by two lines or more in 45 eyes (80.4%), remained unchanged in 8 eyes (14.3%) and worsened in 3 eyes (5.3%). Visual acuity improved to 0.3 or more in 24 eyes (42.9%). Better postoperative visual acuity (0.3 or better) was related to hemoglobin A1C (HbA1C) and the size of hard exudates. Conclusions : Results showed the efficacy of submacular surgery to remove massive hard exudates with diabetic macular edema, and outcomes were satisfactory.

A convergent total synthesis of cytotoxic marine natural polycyclic ether, gymnocin-A (1), is described. The synthesis features three iterations of an oxiranyl anion strategy, involving base-mediated cycloetherification, ring expansion, and reductive etherification, for the construction of the FGH fragment and for its coupling with the ABC and KLMN fragments.