Plan comparison of prostate stereotactic radiotherapy in spacer implant patients.

In prostate stereotactic body radiation therapy (SBRT), hydrogel spacers are increasingly used. This study aimed to perform a dosimetry comparison of treatment plans using CyberKnife (CK), commonly used for prostate SBRT, Helical TomoTherapy (HT), and TrueBeam (TB) in patients with hydrogel spacer implantations. The data of 20 patients who received hydrogel spacer implantation for prostate SBRT were retrospectively analyzed. The prescription dose was 36.25 Gy in five fractions to 95% of the planning target volume (PTV; D95). The conformity index (CI), gradient index (GI), homogeneity index (HI), and dose-volume histogram (DVH) were analyzed for the three modalities, using the same PTV margins. The monitor unit (MU) and the beam-on-time (BOT) values were subsequently compared. The CI of TB (0.93 ± 0.02) was significantly superior to those of CK (0.82 ± 0.03, p < 0.01) and HT (0.86 ± 0.03, p < 0.01). Similarly, the GI value of TB (3.59 ± 0.12) was significantly better than those of CK (4.31 ± 0.43, p < 0.01) and HT (4.52 ± 0.24, p < 0.01). The median doses to the bladder did not differ between the CK and TB (V18.1 Gy: 16.5% ± 4.5% vs. 15.8% ± 4.4%, p = 1.00), but were significantly higher for HT (V18.1 Gy: 33.2% ± 7.3%, p < 0.01 vs. CK, p < 0.01 vs. TB). The median rectal dose was significantly lower for TB (V18.1 Gy: 5.6% ± 4.5%) than for CK (V18.1 Gy: 11.2% ± 6.7%, p < 0.01) and HT (20.2% ± 8.3%, p < 0.01). TB had the shortest BOT (2.6 min; CK: 17.4 min, HT: 6.9 min). TB could create treatment plans dosimetrically comparable to those of CK when using the same margins, in patients with hydrogel spacers.

Endogenous Endophthalmitis successfully treated with Intravitreal Povidone-iodine injection: a case report.

BACKGROUND: The usefulness of povidone-iodine as an alternative to antimicrobial agents, for endophthalmitis, has recently been documented. We report a case of endogenous endophthalmitis successfully treated with intravitreal injection of povidone-iodine. CASE PRESENTATION: An 88-year-old woman underwent small bowel bypass surgery for postoperative ileus following rectal cancer resection. She developed a fever during total parenteral nutrition and was diagnosed with gram-positive cocci bacteremia of central venous catheter origin. The patient was referred to our department with chief complaints of ocular pain, hyperemia and decreased vision in the right eye, which had manifested during the febrile period. The initial examination revealed the visual acuity in her right eye to be finger counting and that in her left eye 0.2. The right eye showed a severe inflammatory reaction in the anterior chamber, fibrin deposition, and hypopyon. The fundus was difficult to visualize. Endogenous endophthalmitis due to bacteria was diagnosed. Surgical treatment was judged to be difficult based on the patient's poor general condition and mental status, and intravitreal injection of 0.1 ml of 1.25% povidone-iodine was performed on the same day. The inflammation rapidly diminished, and the hypopyon had disappeared 4 days after treatment. The fundus became visible 7 days after treatment and there was no recurrence of endophthalmitis findings. The visual acuity in her right eye recovered to that in the left eye (0.2). CONCLUSION: Intravitreal injection of povidone-iodine is potentially useful and effective as an alternative treatment of antibiotics for endogenous endophthalmitis patients, especially in whom surgical therapy is difficult.

Derivatization of inhibitor of apoptosis protein (IAP) ligands yields improved inducers of estrogen receptor α degradation.

Aberrant expression of proteins often underlies many diseases, including cancer. A recently developed approach in drug development is small molecule-mediated, selective degradation of dysregulated proteins. We have devised a protein-knockdown system that utilizes chimeric molecules termed specific and nongenetic IAP-dependent protein erasers (SNIPERs) to induce ubiquitylation and proteasomal degradation of various target proteins. SNIPER(ER)-87 consists of an inhibitor of apoptosis protein (IAP) ligand LCL161 derivative that is conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen by a PEG linker, and we have previously reported that this SNIPER efficiently degrades the ERα protein. Here, we report that derivatization of the IAP ligand module yields SNIPER(ER)s with superior protein-knockdown activity. These improved SNIPER(ER)s exhibited higher binding affinities to IAPs and induced more potent degradation of ERα than does SNIPER(ER)-87. Further, they induced simultaneous degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) and delayed degradation of X-linked IAP (XIAP). Notably, these reengineered SNIPER(ER)s efficiently induced apoptosis in MCF-7 human breast cancer cells that require IAPs for continued cellular survival. We found that one of these molecules, SNIPER(ER)-110, inhibits the growth of MCF-7 tumor xenografts in mice more potently than the previously characterized SNIPER(ER)-87. Mechanistic analysis revealed that our novel SNIPER(ER)s preferentially recruit XIAP, rather than cIAP1, to degrade ERα. Our results suggest that derivatized IAP ligands could facilitate further development of SNIPERs with potent protein-knockdown and cytocidal activities against cancer cells requiring IAPs for survival.

Prospective study of vitrectomy for epiretinal membranes in patients with good best-corrected visual acuity.

BACKGROUND: To evaluate the efficacy of epiretinal membrane removal in patients with good best-corrected visual acuity (BCVA) for improving visual function and quality of life (QOL). METHODS: This prospective case study compared 37 subjects with preoperative BCVA ≦ 0.046 logMAR (Good group) to 35 patients with 0.10-0.52 logMAR (Moderate group) at 3 and 6 months. Linear mixed-effect models were used for statistical analysis. The primary outcome was the horizontal metamorphopsia score (MH) at 6 months postoperatively (post-6 M), while secondary outcomes were postoperative BCVA, vertical metamorphopsia score (MV), aniseikonia, stereopsis and central foveal thickness. In the Good group, QOL was assessed using the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) at 6 and 12 months. RESULTS: MH was significantly improved at post-3 M and post-6 M in the both groups but there were no significant differences between the two groups. MV showed no improvement at the final observation in either group. LogMAR BCVA was significantly improved at post-6 M in the Good group, which had significantly better vision than the Moderate group. Preoperative vertical and horizontal aniseikonia scores remained unchanged in the Good group at post-6 M but worsened in the Moderate group. The NEI VFQ-25 score improved in the Good group, reflecting improved general health, general vision, and mental health. CONCLUSIONS: Early epiretinal surgery for patients with BCVA ≦ 0.046 logMAR was effective for improvement of HM, BCVA, and QOL and prevented worsening of aniseikonia. TRIAL REGISTRATION: UMIN000021220 . Registered 10 September 2015. UMIN Clinical Trials Registry.

Development of a Potent Protein Degrader against Oncogenic BCR-ABL Protein.

Chromosomal translocation occurs in some cancer cells, resulting in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative approach to treat CML is to downregulate expression of the BCR-ABL protein. Recently, we have devised a protein knockdown system by hybrid molecules named Specific and Nongenetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers (SNIPER). This system is designed to induce IAP-mediated ubiquitylation and proteasomal degradation of target proteins. In this review, we describe the development of SNIPER against BCR-ABL, and discuss the features and prospect for treatment of CML.

Different Degradation Mechanisms of Inhibitor of Apoptosis Proteins (IAPs) by the Specific and Nongenetic IAP-Dependent Protein Eraser (SNIPER).

Targeted protein degradation by small molecules is an emerging modality with significant potential for drug discovery. We previously developed chimeric molecules, termed specific and non-genetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs), which induce the ubiquitylation and proteasomal degradation of target proteins. This degradation is mediated by the IAPs; the target proteins include bromodomain-containing protein 4 (BRD4), an epigenetic regulator protein. The SNIPER that degrades this particular protein, SNIPER(BRD)-1, consists of an IAP antagonist LCL-161 derivative and a bromodomain and extra-terminal (BET) inhibitor, (+)-JQ-1. SNIPER(BRD)-1 also degrades a cellular inhibitor of apoptosis protein 1 (cIAP1) and an X-linked inhibitor of apoptosis protein (XIAP), the mechanisms of which are not well understood. Here, we show that the degradation of cIAP1 and XIAP by SNIPER(BRD)-1 is induced via different mechanisms. Using a chemical biology-based approach, we developed two inactive SNIPERs, SNIPER(BRD)-3 and SNIPER(BRD)-4, incapable of degrading BRD4. SNIPER(BRD)-3 contained an N-methylated LCL-161 derivative as the IAP ligand, which prevented it from binding IAPs, and resulted in the abrogated degradation of cIAP1, XIAP, and BRD4. SNIPER(BRD)-4, however, incorporated the enantiomer (-)-JQ-1 which was incapable of binding BRD4; this SNIPER degraded cIAP1 but lost the ability to degrade XIAP and BRD4. Furthermore, a mixture of the ligands, (+)-JQ-1 and LCL-161, induced the degradation of cIAP1, but not XIAP and BRD4. These results indicate that cIAP1 degradation is triggered by the binding of the IAP antagonist module to induce autoubiquitylation of cIAP1, whereas a ternary complex formation is required for the SNIPER-induced degradation of XIAP and BRD4.

In Vivo Knockdown of Pathogenic Proteins via Specific and Nongenetic Inhibitor of Apoptosis Protein (IAP)-dependent Protein Erasers (SNIPERs).

Many diseases, especially cancers, result from aberrant or overexpression of pathogenic proteins. Specific inhibitors against these proteins have shown remarkable therapeutic effects, but these are limited mainly to enzymes. An alternative approach that may have utility in drug development relies on selective degradation of pathogenic proteins via small chimeric molecules linking an E3 ubiquitin ligase to the targeted protein for proteasomal degradation. To this end, we recently developed a protein knockdown system based on hybrid small molecule SNIPERs (Specific and Nongenetic IAP-dependent Protein Erasers) that recruit inhibitor of the apoptosis protein (IAP) ubiquitin ligases to specifically degrade targeted proteins. Here, we extend our previous study to show a proof of concept of the SNIPER technology in vivo By incorporating a high affinity IAP ligand, we developed a novel SNIPER against estrogen receptor α (ERα), SNIPER(ER)-87, that has a potent protein knockdown activity. The SNIPER(ER) reduced ERα levels in tumor xenografts and suppressed the growth of ERα-positive breast tumors in mice. Mechanistically, it preferentially recruits X-linked IAP (XIAP) rather than cellular IAP1, to degrade ERα via the ubiquitin-proteasome pathway. With this IAP ligand, potent SNIPERs against other pathogenic proteins, BCR-ABL, bromodomain-containing protein 4 (BRD4), and phosphodiesterase-4 (PDE4) could also be developed. These results indicate that forced ubiquitylation by SNIPERs is a useful method to achieve efficient protein knockdown with potential therapeutic activities and could also be applied to study the role of ubiquitylation in many cellular processes.

Design and synthesis of cell-permeable fluorescent nitrilotriacetic acid derivatives.

Fluorescence labeling of the target molecules using a small molecule-based probe is superior than a method using genetically expressed green fluorescence protein (GFP) in terms of convenience in its preparation and functionalization. Fluorophore-nitrilotriacetic acid (NTA) conjugates with several ester protecting groups were synthesized and evaluated for their cell membrane permeability by fluorescence microscopy analysis. One of the derivatives, acetoxymethyl (AM)-protected NTA conjugate is hydrolyzed, resulting in intracellular accumulation, thus providing localized fluorescence intensity in cells. This modification is expected as an effective method for converting a non-cell membrane permeable NTA-BODIPY conjugates to a cell membrane permeable derivatives.

Acquired Resistance to Shiga Toxin-Induced Apoptosis by Loss of CD77 Expression in Human Myelogenous Leukemia Cell Line, THP-1.

Shiga toxin (Stx) is a main virulence factor of Enterohemorrhagic Escherichia coli (EHEC) that causes diarrhea and hemorrhagic colitis and occasionally fatal systemic complications. Stx induces rapid apoptotic cell death in some cells, such as human myelogenous leukemia THP-1 cells expressing CD77, a receptor for Stx internalization, and the induction of apoptotic cell death is thought to be crucial for the fatal systemic complications. Therefore, in order to suppress the fatal toxicity, it is important to understand the mechanism how cells can escape from apoptotic cell death in the presence of Stx. In this study, we isolated resistant clones to Stx-induced apoptosis from highly sensitive THP-1 cells by continuous exposure with lethal dose of Stx. All of the ten resistant clones lost the expression of CD77 as a consequence of the reduction in CD77 synthase mRNA expression. These results suggest that downregulation of CD77 or CD77 synthase expression could be a novel approach to suppress the fatal toxicity of Stx in EHEC infected patient.

Targeted Degradation of Proteins Localized in Subcellular Compartments by Hybrid Small Molecules.

Development of novel small molecules that selectively degrade pathogenic proteins would provide an important advance in targeted therapy. Recently, we have devised a series of hybrid small molecules named SNIPER (specific and nongenetic IAP-dependent protein ERaser) that induces the degradation of target proteins via the ubiquitin-proteasome system. To understand the localization of proteins that can be targeted by this protein knockdown technology, we examined whether SNIPER molecules are able to induce degradation of cellular retinoic acid binding protein II (CRABP-II) proteins localized in subcellular compartments of cells. CRABP-II is genetically fused with subcellular localization signals, and they are expressed in the cells. SNIPER(CRABP) with different IAP-ligands, SNIPER(CRABP)-4 with bestatin and SNIPER(CRABP)-11 with MV1 compound, induce the proteasomal degradation of wild-type (WT), cytosolic, nuclear, and membrane-localized CRABP-II proteins, whereas only SNIPER(CRABP)-11 displayed degradation activity toward the mitochondrial CRABP-II protein. The small interfering RNA-mediated silencing of cIAP1 expression attenuated the knockdown activity of SNIPER(CRABP) against WT and cytosolic CRABP-II proteins, indicating that cIAP1 is the E3 ligase responsible for degradation of these proteins. Against membrane-localized CRABP-II protein, cIAP1 is also a primary E3 ligase in the cells, but another E3 ligase distinct from cIAP2 and X-linked inhibitor of apoptosis protein (XIAP) could also be involved in the SNIPER(CRABP)-11-induced degradation. However, for the degradation of nuclear and mitochondrial CRABP-II proteins, E3 ligases other than cIAP1, cIAP2, and XIAP play a role in the SNIPER-mediated protein knockdown. These results indicate that SNIPER can target cytosolic, nuclear, membrane-localized, and mitochondrial proteins for degradation, but the responsible E3 ligase is different, depending on the localization of the target protein.

SNIPER(TACC3) induces cytoplasmic vacuolization and sensitizes cancer cells to Bortezomib.

We previously developed a hybrid small molecule SNIPER (Specific and Nongenetic IAP-dependent Protein ERaser) against transforming acidic coiled-coil-3 (TACC3), SNIPER(TACC3), that induces proteasomal degradation of TACC3 protein. In this study, we found that SNIPER(TACC3) induces cytoplasmic vacuolization derived from endoplasmic reticulum (ER) and paraptosis-like cell death selectively in cancer cells. Mechanistic analysis suggests that accumulation of ubiquitylated protein aggregates that requires X-linked inhibitor of apoptosis protein (XIAP) induces ER stress, which results in ER-stress responses involving X-box binding protein-1 (XBP-1) and ER-derived vacuolization in cancer cells. Importantly, inhibition of proteasome enhanced the SNIPER(TACC3)-induced vacuolization, and the combination treatment of SNIPER(TACC3) and bortezomib exhibited a synergistic anticancer activity in several cancer cell lines. The induction of paraptosis-like cell death in cancer cells by SNIPER(TACC3) could be applied to treat cancer cells resistant to undergo apoptosis by overexpression of XIAP.

Development of protein degradation inducers of oncogenic BCR-ABL protein by conjugation of ABL kinase inhibitors and IAP ligands.

Chromosomal translocation occurs in some cancer cells, which results in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative approach to treat CML is to downregulate the BCR-ABL protein. We have devised a protein knockdown system by hybrid molecules named Specific and Non-genetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers (SNIPER), which is designed to induce IAP-mediated ubiquitylation and proteasomal degradation of target proteins, and a couple of SNIPER(ABL) against BCR-ABL protein have been developed recently. In this study, we tested various combinations of ABL inhibitors and IAP ligands, and the linker was optimized for protein knockdown activity of SNIPER(ABL). The resulting SNIPER(ABL)-39, in which dasatinib is conjugated to an IAP ligand LCL161 derivative by polyethylene glycol (PEG) × 3 linker, shows a potent activity to degrade the BCR-ABL protein. Mechanistic analysis suggested that both cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) play a role in the degradation of BCR-ABL protein. Consistent with the degradation of BCR-ABL protein, the SNIPER(ABL)-39 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and Crk like proto-oncogene (CrkL), and suppressed the growth of BCR-ABL-positive CML cells. These results suggest that SNIPER(ABL)-39 could be a candidate for a degradation-based novel anti-cancer drug against BCR-ABL-positive CML.

M-COPA, a novel Golgi system disruptor, suppresses apoptosis induced by Shiga toxin.

Shiga toxin (Stx) is a main virulence factor of Stx-producing Escherichia coli (STEC) that contributes to diarrhea and hemorrhagic colitis and occasionally to fatal systemic complications. Therefore, the development of an antidote to neutralize Stx toxicity is urgently needed. After internalization into cells, Stx is transferred to the Golgi apparatus via a retrograde vesicular transport system. We report here that 2-methylcoprophilinamide (M-COPA), a compound that induces disassembly of the Golgi apparatus by inactivating ADP-ribosylation factor 1 (Arf1), suppresses Stx-induced apoptosis. M-COPA inhibited transport of Stx from the plasma membrane to the Golgi apparatus and suppressed degradation of anti-apoptotic proteins and the activation of caspases. These findings suggest that inhibition of Stx retrograde transport by M-COPA could be a novel approach to suppress Stx toxicity.

Simple and efficient knockdown of His-tagged proteins by ternary molecules consisting of a His-tag ligand, a ubiquitin ligase ligand, and a cell-penetrating peptide.

We designed and synthesized hybrid molecules for a protein knockdown method based on the recognition of a His-tag fused to a protein of interest (POI). The synthesized target protein degradation inducers contained three functional moieties: a His-tag ligand (nickel nitrilotriacetic acid [Ni-NTA]), an E3 ligand (bestatin [BS] or MV1), and a carrier peptide (Tat or nonaarginine [R9]). The designed hybrid molecules, BS-Tat-Ni-NTA, MV1-Tat-Ni-NTA, BS-R9-Ni-NTA, and MV1-R9-Ni-NTA, efficiently degraded His-tagged cellular retinoic acid binding protein 2 via the ubiquitin-proteasome system (UPS). This system will become a useful tool for research into selective protein degradation inducers that act via the UPS.

A Helix-Stabilized Cell-Penetrating Peptide as an Intracellular Delivery Tool.

Two types of cationic cyclic α,α-disubstituted α-amino acids: ApiC2NH2 (which possesses a lysine mimic side chain) and Api(C2Gu) (which possesses an arginine mimic side chain), were developed. These amino acids were incorporated into an arginine-based peptide sequence [(L-Arg-L-Arg-dAA)3: dAA=ApiC2NH2 or Api(C2Gu)], and the relationship between the secondary structures of the resulting peptides and their ability to pass through cell membranes was investigated. The peptide containing Api(C2Gu) formed a stable α-helical structure and was more effective at penetrating cells than the nonhelical Arg nonapeptide (R9). Furthermore, the peptide was able to deliver plasmid DNA into various types of cells in a highly efficient manner.

Development of BCR-ABL degradation inducers via the conjugation of an imatinib derivative and a cIAP1 ligand.

The manipulation of protein stability with small molecules has great potential as a technique for aiding the development of clinical therapies, including treatments for cancer. In this study, BCR-ABL protein degradation inducers called SNIPER(ABL) (Specific and Non-genetic inhibitors of apoptosis protein [IAP]-dependent Protein Erasers) were developed. The designed molecules contained two biologically active scaffolds: one was an imatinib derivative that binds to BCL-ABL and the other was a methyl bestatin that binds to cellular IAP 1 (cIAP1). The hybrid molecules, SNIPER(ABL), were expected to recruit BCR-ABL to cIAP1 for removal by proteasomes. In fact, SNIPER(ABL) induced the degradation of BCR-ABL protein and a subsequent reduction in cell growth. Thus, the degradation of BCR-ABL by SNIPER(ABL) is one potential strategy for treating BCR-ABL driven chronic myelogenous leukemia.

Interaction between RB protein and NuMA is required for proper alignment of spindle microtubules.

Retinoblastoma protein (pRB) controls cell cycle progression and cell cycle exit through interactions with cellular proteins. Many pRB-binding proteins, which function in gene transcription or modulation of chromatin structure, harbor LXCXE motifs in their binding domain for pRB. In this study, we found that nuclear mitotic apparatus protein (NuMA), a mitotic spindle organizer, interacts with pRB through LSCEE sequences located in its C-terminal region. siRNA-mediated down-regulation of pRB caused aberrant distribution of NuMA and alignment of spindle microtubules in mitotic cells. Abnormal organization of spindle microtubules was also accompanied by misalignment of an over-expressed NuMA mutant (mut-NuMA) with a defect in pRB binding caused by an LSGEK mutation. The mut-NuMA-over-expressing cells showed lower potency for survival than wild-type NuMA (wt-NuMA)-over-expressing cells during 2 weeks of culture. Interestingly, knockdown of pRB reduced the population of wt-NuMA-over-expressing cells to the same level as mut-NuMA cells after 2 weeks. Taken together, pRB may have a novel function in regulating the mitotic function of NuMA and spindle organization, which are required for proper cell cycle progression.

Piezo-actuated parallel mechanism for biological cell release at high speed.

In this paper, a dynamic releasing approach is proposed for high-speed biological cell manipulation. A compact parallel mechanism for grasping and releasing microobjects is used to generate controllable vibration to overcome the strong adhesion forces between the end effector and the manipulated object. To reach the required acceleration of the end effector, which is necessary for the detachment of the target object by overcoming adhesion forces, vibration in the end effector is generated by applying sinusoidal voltage to the PZT actuator of the parallel mechanism. For the necessary acceleration, we focus on the possible range of the frequency of the PZT-actuator-induced vibration, while minimizing the amplitude of the vibration (14 nm) to achieve precise positioning. The effect of the air and liquid environments on the required vibration frequency for successful release is investigated. For the first time, release results of microbeads and biological cells are compared. Release of the biological cells with 100 % success rate suggests that the proposed active release method is an appropriate solution for adhered biological cells during the release task.

RANDOMIZED CONTROLLED STUDY OF INTRAVITREAL BEVACIZUMAB 0.16 MG INJECTED ONE DAY BEFORE SURGERY FOR PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To investigate the usefulness of 0.16 mg/0.05 mL intravitreal bevacizumab (IVB) injection 1 day before vitrectomy for proliferative diabetic retinopathy. METHODS: Sixty-two patients with proliferative diabetic retinopathy (66 eyes) with an indication for primary vitrectomy were randomized to IVB group (34 eyes) or sham control group (32 eyes). Intravitreal bevacizumab group received intravitreal injection of 0.16 mg/0.05 mL bevacizumab, and sham control group received sham injection 1 day before vitrectomy. Vitreous fluid was sampled before vitrectomy was started. RESULTS: Frequency of reoperation due to recurrent vitreous hemorrhage within 4 weeks after surgery was significantly lower (P = 0.033) in IVB group (3.1%, 1/32) than in sham control group (20.6%, 7/34). The number of intraoperative endodiathermy spots (0.63 ± 1.0 vs. 1.3 ± 1.4, P = 0.025) and frequency of postoperative recurrent vitreous hemorrhage (3.1%, 1/32 vs. 23.5%, 8/34, P = 0.017) were significantly lower in IVB group than in sham control group. Vitreous vascular endothelial growth factor concentrations were 1315.3 ± 1153.4 pg/mL in sham control group and 25.0 ± 13.6 pg/mL in IVB group (P < 0.0001). CONCLUSION: Intravitreal injection of 0.16 mg/0.05 mL bevacizumab 1 day before vitrectomy blocked vascular endothelial growth factor production in vitreous and significantly reduced the incidence of reoperation due to early postoperative recurrent vitreous hemorrhage.

Vitrectomy using 0.025% povidone-iodine in balanced salt solution plus for the treatment of postoperative endophthalmitis.

PURPOSE: To investigate the bactericidal effect of 0.025% povidone-iodine in Balanced Salt Solution PLUS (0.025% PI-BSS PLUS) and its use in vitrectomy for postoperative endophthalmitis. METHODS: First, an experimental laboratory model using Staphylococcus aureus was used to evaluate the bactericidal effect of PI-BSS PLUS. Next, in a case series of 4 eyes with postoperative endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS as irrigation solution was conducted, followed by postoperative intravitreal and intravenous antibiotics. RESULTS: In in vitro study, PI at concentrations of 0.01% and above in BSS PLUS exhibited marked bactericidal effect after 15 seconds of exposure. Bactericidal effect of 0.025% PI-BSS PLUS was maintained at room temperature storage for 15 minutes but was attenuated after 30 minutes. Among 4 eyes that underwent vitrectomy using 0.025% PI-BSS PLUS, coagulase-negative Staphylococcus sp. was isolated in 1 eye at the beginning but not at completion of surgery. In all four eyes, endophthalmitis was resolved with no adverse events. Ocular toxicity was not observed. CONCLUSION: The 0.025% PI-BSS PLUS is bactericidal and nontoxic when used as irrigation solution in vitrectomy. In 4 cases of postoperative endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS followed by postoperative antibiotics resolved endophthalmitis.