Enzyme-like Regiodivergent Behavior of a Flavopeptide Catalyst in Aerobic Baeyer-Villiger Oxidation.

We recently developed a flavopeptide immobilized on polystyrene resin, Fl-Pep-PS, that could realize the first N5-unmodified neutral flavin (Fl)-catalyzed aerobic oxygenation reactions under non-enzymatic conditions. Although a key active species is assumed to be the corresponding 4a-hydroperoxyflavin (Fl4aOOH) from the unprecedented activity and unique chemoselectivity, further circumstantial support would be helpful to be sure since spectroscopic evidence is difficult to obtain due to the compound's insolubility. In this article, we report that the aerobic Baeyer-Villiger oxidation of a fused cyclobutanone, (±)-cis-bicyclo[3.2.0]hept-2-en-6-one (1), can be promoted with Fl-Pep-PS in a FMO-like chemoselectivity and regiodivergent manner via Fl-related catalytic intermediates, which delivers strong evidence of the involvement of Fl4aOOH as an active species in Fl-Pep-PS-catalyzed aerobic oxygenation reactions.

Long-term outcomes of visual field defects after indocyanine green-assisted macular hole surgery.

PURPOSE: To evaluate the long-term course of visual field defects after intravitreal injection of indocyanine green (ICG) during vitrectomy. METHODS: Retrospective observational case series. The medical records of seven eyes of seven patients with visual field defects after the adjunctive use of ICG during macular hole surgery were studied. All of the surgeries were performed between February 2001 and January 2002. Humphrey static perimetry and best-corrected visual acuity were examined periodically, and the main outcome measure was the mean deviation (MD) determined by the Humphrey (30-2) SITA-Fast program. RESULTS: All patients were observed for more than 4.5 years, for a mean of 60.7 months and a range of 54 to 66 months. The preoperative MD was -3.5 +/- 3.1 dB (mean +/- SD), and the postoperative MD was -13.3 +/- 4.9 dB at 1 year, -13.4 +/- 4.6 dB at 2 years, -16.2 +/- 5.1 dB at 3 years, and -15.6 +/- 5.1 dB at 4 years. The decrease in the mean MD between 1 and 3 years after surgery was significant (P < 0.05). Optic disk pallor in five eyes showed a decrease in the MD between 1 year and 3 years after the surgery. There was no significant difference in the postoperative best-corrected visual acuity at any time. CONCLUSIONS: The visual field defect in eyes that had undergone vitrectomy with staining of the internal limiting membrane with ICG can continue to deteriorate for at least 3 years. Eyes receiving intravitreal ICG during vitrectomy should be followed for a longer period to determine the long-term effect of ICG.

Intraocular pressure after intravitreal injection of triamcinolone acetonide following vitrectomy for macular edema.

PURPOSE: To evaluate long-term intraocular pressure (IOP) response after intravitreal injections of different doses of triamcinolone acetonide (TA) upon completion of pars plana vitrectomy (PPV) for macular edema secondary to diabetic retinopathy or retinal vein occlusion. PATIENTS AND METHODS: Retrospective, consecutive, comparative, interventional case series. Twenty-seven eyes of 25 consecutive patients with macular edema associated with diabetic retinopathy (n=18) or retinal vein occlusion (n=9), who underwent PPV for the treatment of macular edema between January 2003 and December 2003, were included. Upon completion of vitrectomy, different doses of TA were injected into the vitreous cavity: 14 eyes with 5 mg of TA (group 1) and 13 eyes with 10 mg of TA (group 2). The main outcome measure was IOP. RESULTS: All patients were followed up for at least 12 months. Preoperative IOP was 12.6+/-2.6 mm Hg (mean+/-standard deviation) in group 1 and 13.2+/-2.1 mm Hg in group 2. Postoperatively, IOP increased to a mean maximum of 20.6+/-5.5 mm Hg in group 1 and 31.5+/-3.5 mm Hg in group 2 (P<0.01 for both groups). The difference between groups was also significant (P<0.05). Five of 14 eyes (36%) in group 1 and 10 of 13 eyes (77%) in group 2 had an elevation of IOP exceeding 21 mm Hg (P=0.03). The median interval from surgery to reach maximal IOP was 7 days in both groups. The significant IOP elevation lasted for 3 months in group 1 and 6 months in group 2. CONCLUSIONS: After injecting of TA into the vitreous cavity upon completion of PPV for macular edema, a dose-dependent IOP elevation was observed, starting from early postoperative days and returning to normal values after several months. These results show that intravitreal TA injection in the vitrectomized eyes might have different IOP changes from in the nonvitrectomized eyes.

Design of peptide-containing N5-unmodified neutral flavins that catalyze aerobic oxygenations.

Simulation of the monooxygenation function of flavoenzyme (Fl-Enz) has been long-studied with N5-modified cationic flavins (FlEt+ ), but never with N5-unmodified neutral flavins (Fl) despite the fact that Fl is genuinely equal to the active center of Fl-Enz. This is because of the greater lability of 4a-hydroperoxy adduct of Fl, FlOOH , compared to those of FlEt+ , FlEtOOH , and Fl-Enz, FlOOH-Enz. In this study, Fl incorporated into a short peptide, flavopeptide (Fl-Pep), was designed by a rational top-down approach using a computational method, which could stabilize the corresponding 4a-hydroperoxy adduct (FlOOH-Pep) through intramolecular hydrogen bonds. We report catalytic chemoselective sulfoxidation as well as Baeyer-Villiger oxidation by means of Fl-Pep under light-shielding and aerobic conditions, which are the first Fl-Enz-mimetic aerobic oxygenation reactions catalyzed by Fl under non-enzymatic conditions.

Analysis of the retinal nerve fiber layer after indocyanine green-assisted vitrectomy for idiopathic macular holes.

PURPOSE: To analyze retinal nerve fiber layer (RNFL) thickness in eyes with or without visual field (VF) defects after indocyanine green-assisted vitrectomy for idiopathic macular holes using optical coherence tomography (OCT) and to investigate the relationship between postoperative VF defects and RNFL damage. DESIGN: Retrospective interventional case series. PARTICIPANTS: Thirty-four eyes of 32 patients with idiopathic macular holes that underwent vitrectomy between January 2001 and March 2003 were included in this study. Eyes were divided into 3 groups according to the occurrence of postoperative VF defects and the use of indocyanine green for internal limiting membrane peeling during surgery: 11 eyes with VF defects after indocyanine green-assisted vitrectomy (group 1), 9 eyes without VF defects despite the use of indocyanine green (group 2), and 14 eyes without VF defects that underwent vitrectomy without indocyanine green (group 3). METHODS: Retinal nerve fiber layer thickness in each of 4 quadrants (superior, inferior, nasal, temporal) was measured with OCT. MAIN OUTCOME MEASURE: Retinal nerve fiber layer thickness around the optic disc. RESULTS: The mean RNFL thickness in 3 of 4 quadrants (superior, nasal, inferior) in group 1 was significantly less than that in the corresponding quadrant in groups 2 and 3 (P<0.01). In the temporal quadrant, there was a significant difference between groups 1 and 3 (P = 0.02), but not between groups 1 and 2. The RNFL thickness in group 1 was significantly less in 3 quadrants in operated eyes than in fellow eyes (P<0.05). CONCLUSIONS: The RNFL thickness was reduced in eyes with VF defects after indocyanine green-assisted vitrectomy for macular holes, suggesting that the postoperative VF defects may have been caused by RNFL damage relating to the use of indocyanine green.

Visual field defects after intravitreous administration of indocyanine green in macular hole surgery.

OBJECTIVES: To report the findings on a patient cohort with visual field defects after macular hole surgery with indocyanine green (ICG)-assisted internal limiting membrane peeling and to investigate the correlation between the defects and the use of ICG. DESIGN: Retrospective, noncomparative interventional case series. PARTICIPANTS: Thirty-nine eyes of 38 patients having the clinical diagnosis of a macular hole who underwent pars plana vitrectomy between January 1, 2001, and December 31, 2002, were enrolled in this study. INTERVENTION: Indocyanine green-assisted internal limiting membrane peeling was performed on a series of 22 eyes: 12 eyes using a 0.5% ICG solution and 3-minute exposure to the retina (group 1), 4 eyes using a 0.5% ICG solution and immediate washout (group 2), and 6 eyes using a 0.25% ICG solution and immediate washout (group 3). The remaining 17 eyes underwent vitrectomy without ICG-assisted internal limiting membrane peeling (group 4). MAIN OUTCOME MEASURES: Visual field, best-corrected visual acuity, and fundus photography were evaluated. RESULTS: Postoperatively, all patients (100%) in group 1 and 1 (25%) of 4 eyes in group 2 had visual field defects. None of the patients in group 3 had a visual field defect. The visual field defects included 10 eyes (84%) with nasal defects, 1 eye (8%) with an inferotemporal defect, and 1 eye (8%) with an extensive visual field defect. Ophthalmoscopy revealed mild to moderate optic disc pallor in 8 (62%) of 13 eyes with postoperative visual field defects. Only 1 patient in group 4 had an inferotemporal defect; none of the other patients in group 4 had visual field defects. There was no statistically significant difference in postoperative visual acuity between patients with and without postoperative visual field defects. CONCLUSIONS: Although this study was limited by the few patients enrolled, our experience indicates that visual field defects, specifically nasal defects, can occur after macular hole surgery with ICG-assisted internal limiting membrane peeling, and that the incidence depends on the concentration of the ICG solution and/or the exposure time to the retina. Further studies are needed to clarify the pathomechanism of visual field defects.

Vitrectomy with internal limiting membrane peeling for macular retinoschisis and retinal detachment without macular hole in highly myopic eyes.

PURPOSE: To report anatomic and visual improvement following vitrectomy with internal limiting membrane (ILM) peeling for two highly myopic patients with retinoschisis and/or retinal detachment without a macular hole. DESIGN: Two interventional case reports. METHODS: Two highly myopic patients who had retinoschisis and/or retinal detachment without a full-thickness macular hole underwent vitrectomy, internal limiting membrane peeling, and long-acting gas injection. Main outcome measures included best-corrected visual acuity, biomicroscopic appearance, and optical coherent tomography finding. RESULTS: Vitrectomy with ILM peeling results in biomicroscopic, functional, and tomographic improvement in both patients, for follow-up periods of 12 months and 8 months, respectively. CONCLUSIONS: Vitrectomy with ILM peeling and gas tamponade is an effective method for retinoschisis and/or retinal detachment without a macular hole in highly myopic patients.

Visual field defects after uneventful vitrectomy for epiretinal membrane with indocyanine green-assisted internal limiting membrane peeling.

PURPOSE: To report visual field defects after vitrectomy for epiretinal membrane with indocyanine green (ICG)-assisted internal limiting membrane (ILM) peeling. DESIGN: Interventional consecutive case series. METHODS: A retrospective review of 16 eyes of 16 patients who underwent vitrectomy for idiopathic epiretinal membrane. Indocyanine green-assisted ILM peeling was performed in 7 of 16 eyes. The main outcome measure was postoperative visual field. RESULTS: Four of seven eyes (57%) with ICG-assisted ILM peeling had visual field defects postoperatively. The field defects identified were nasal in three eyes; in the fourth eye, the visual field was constricted to approximately 30 degrees. None of the nine eyes without ICG-assisted ILM peeling had a visual field defect. CONCLUSIONS: Peripheral visual field defects may occur after vitrectomy with ICG-assisted ILM peeling. Although the cause of the defects is unclear, the potential role of ICG toxicity requires further investigation.