Sutured scleral fixation of existing subluxated/dislocated acrylic one-piece intraocular lenses.

AIM: To evaluate the visual and refractive outcomes in cases after sutured scleral fixation of existing subluxated or dislocated acrylic one-piece intraocular lenses (IOLs). METHODS: This study retrospectively enrolled a consecutive series of patients who underwent a surgery of sutured existing subluxated or dislocated IOLs from October 2018 to June 2020. All patients underwent comprehensive preoperative and postoperative ophthalmologic examination, and data were collected including age, sex, surgical indications, best-corrected visual acuity, refractive error, intraocular pressure. Presence of intraoperative and postoperative surgical complications was documented. RESULTS: A total of 20 consecutive cases were enrolled for analysis with mean final follow-up period 9.8±5.3mo. Visual acuity improved from a mean of 0.35 (0.46±0.32 logMAR) preoperatively to 0.61 (0.21±0.18 logMAR) at the 3-month follow-up (P=0.002). The mean amount of preoperative keratometric astigmatism and total postoperative refractive astigmatism was -1.24±0.80 diopters (D) and -1.42±0.97 D, respectively. There was no statistically significant difference between preoperative and postoperative astigmatism (P=0.156). The mean IOL-induced astigmatism was -0.23±0.53 D. The mean spherical equivalent at the 3-month follow-up was -0.1±0.94 D. No major complications were noted during the follow-up period. CONCLUSION: Surgical techniques using sutured scleral fixation of existing subluxated or dislocated acrylic one-piece IOLs result in favorable visual and refractive outcomes without major complications.

Using Smartphone Chatbot for Postoperative Care after Intravitreal Injection during COVID-19 Period: A Retrospective Cohort Study.

BACKGROUND: During COVID-19 pandemic period, it was difficult for the patients regular and scheduled follow-up in outpatient department, especially when lock-down. However, early detection of patients with initial infection or other serious conditions after ocular surgeries, such as intravitreous injection (IVI) for age-related macular degeneration (AMD). OBJECTIVE: We accessed a postoperative care chatbot system (PCCS) in smartphone for patients to self-report postoperative symptoms/signs with an instant bidirectional feedback system. METHODS: During the COVID-19 level 3 epidemic alert in July 2021 in Taiwan, the PCCS alerted the patient to report and grade six ocular symptoms/signs associated with ocular inflammation or retinal detachment. Patients used the PCCS for 7 days postoperatively to assess their symptoms/signs per day after receiving an alert. The data automatically collected using a cloud computer system judged the grade and sent messages to medical staff for further medical assistance. User's satisfaction questionnaire was collected on the 7th day. RESULTS: One hundred and eighty-five patients participated in this study. There were 26 reports (3.03%) of symptom grade deterioration (increased blurred vision, eye swelling, nausea, and floater/flash) in 12 patients (6.5%). No gender difference for the earlier medical consultation. One case occurred endophthalmitis and improved after 2 times prompt IVI antibiotics. 87% of patients were satisfied or very satisfied to communicate their symptoms instantly with the app, willing to use it again and considered it could improve quality of care. The incidence of earlier medical consultation is 3.8% (7/185) and the incidence of endophthalmitis is 0.5% (1/185). CONCLUSIONS: The chatbot system, designed for self-reporting postoperative symptoms and providing instant bidirectional feedback on smartphones, could be beneficial for enhancing early medical consultation without gender differences in AMD patients who receiving intravitreal injections. It achieves satisfactory response from patients.

Outcomes and eye care knowledge in rhegmatogenous retinal detachment patients with a history of laser refractive surgery for myopia.

Purpose: To investigate the surgical outcomes and eye care knowledge of patients with rhegmatogenous retinal detachment (RRD) who had previously undergone laser refractive surgery (LRS) for myopia in a myopia epidemic area. Methods: This retrospective study included patients with primary RRD who underwent surgery and had a history of LRS for myopia at a tertiary medical center. Data were reviewed from medical charts to analyse the surgical outcomes. Questions about eye care knowledge and attitude toward myopia and LRS were obtained. Results: A total of 774 patients underwent RRD surgery, among whom 341 (44%) had myopia > -3 dioptres, 66% of whom had high myopia. Thirty eyes of 26 patients had a history of LRS for myopia. The mean age of patients with a history of LRS was significantly lower than that of those without a history of LRS (45.7 ± 2.9 years vs. 53.8 ± 1.0, p < 0.001). The mean pre-LRS spherical equivalent was -8.66 ± 0.92 (range: -3.00--12.00) dioptres. In more than half the patients (n = 15, 57.7%), the interval between LRS and RRD was more than 10 years. The primary retinal reattachment rate was only 60%, whereas the final retinal reattachment rate was 93%. The mean final visual acuity (VA) improved from a 20/286 to 20/105 (p = 0.006). Linear mixed model analysis showed factors of male sex and macular detachment were significant with poor visual outcome (p = 0.046 and 0.008) Eye care knowledge obtained from the 19 RRD patients with history of LRS, 47% of patients (9/19) mistakenly thought that LRS could cure myopia and its complications, and 63% of patients were less willing to visit an ophthalmologist because uncorrected VA improvement after LRS. Eighty-four percent thought that proper knowledge and more education about LRS and myopia for the public are important. Conclusion: In the RRD patients with a history of LRS for myopia, their age was relative younger. Male sex and macular detachment were associated with poor visual outcome. More education with proper knowledge of LRS, myopia and RRD is recommended for the patients to prevent or early detect the occurrence of RRD.

County-Wide Mortality Assessments Attributable to PM2.5 Emissions from Coal Consumption in Taiwan.

Over one-third of energy is generated from coal consumption in Taiwan. In order to estimate the health impact assessment attributable to PM2.5 concentrations emitted from coal consumption in Taiwan. We applied a Gaussian trajectory transfer-coefficient model to obtain county-wide PM2.5 exposures from coal consumption, which includes coal-fired power plants and combined heat and power plants. Next, we calculated the mortality burden attributable to PM2.5 emitted by coal consumption using the comparative risk assessment framework developed by the Global Burden of Disease study. Based on county-level data, the average PM2.5 emissions from coal-fired plants in Taiwan was estimated at 2.03 ± 1.29 (range: 0.32-5.64) µg/m3. With PM2.5 increments greater than 0.1 µg/m3, there were as many as 16 counties and 66 air quality monitoring stations affected by coal-fired plants and 6 counties and 18 monitoring stations affected by combined heat and power plants. The maximum distances affected by coal-fired and combined heat and power plants were 272 km and 157 km, respectively. Our findings show that more counties were affected by coal-fired plants than by combined heat and power plants with significant increments of PM2.5 emissions. We estimated that 359.6 (95% CI: 334.8-384.9) annual adult deaths and 124.4 (95% CI: 116.4-132.3) annual premature deaths were attributable to PM2.5 emitted by coal-fired plants in Taiwan. Even in six counties without power plants, there were 75.8 (95% CI: 60.1-91.5) deaths and 25.8 (95%CI: 20.7-30.9) premature deaths annually attributable to PM2.5 emitted from neighboring coal-fired plants. This study presents a precise and effective integrated approach for assessing air pollution and the health impacts of coal-fired and combined heat and power plants.

Blockage of Autophagy Increases Timosaponin AIII-Induced Apoptosis of Glioma Cells In Vitro and In Vivo.

Timosaponin AIII (TSAIII), a saponin isolated from Anemarrhena asphodeloides and used in traditional Chinese medicine, exerts antitumor, anti-inflammatory, anti-angiogenesis, and pro-apoptotic activity on a variety of tumor cells. This study investigated the antitumor effects of TSAIII and the underlying mechanisms in human glioma cells in vitro and in vivo. TSAIII significantly inhibited glioma cell viability in a dose- and time-dependent manner but did not affect the growth of normal astrocytes. We also observed that in both glioma cell lines, TSAIII induces cell death and mitochondrial dysfunction, consistent with observed increases in the protein expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, cytochrome c, and Mcl-1. TSAIII also activated autophagy, as indicated by increased accumulation of the autophagosome markers p62 and LC3-II and the autolysosome marker LAMP1. LC3 silencing, as well as TSAIII combined with the autophagy inhibitor 3-methyladenine (3MA), increased apoptosis in GBM8401 cells. TSAIII inhibited tumor growth in xenografts and in an orthotopic GBM8401 mice model in vivo. These results demonstrate that TSAIII exhibits antitumor effects and may hold potential as a therapy for glioma.

Changes in retinal sensitivity following inverted internal limiting membrane flap technique for large macular holes.

PURPOSE: The aim of this study was to evaluate the effect of inverted internal limiting membrane (ILM) flap technique and measure the retinal sensitivity using microperimetry-1 (MP-1) test in patients with large macular hole (MH). MATERIALS AND METHODS: We enrolled patients undergoing surgery for idiopathic MHs from January 2016 to October 2019. Only patients having a minimum diameter of idiopathic MH exceeding 500 µm were included in this study. All patients underwent complete preoperative ophthalmologic examinations, optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) measurements. Postoperative OCT and BCVA were evaluated at least 3 months postoperatively. In addition, these patients also received MP-1 pre- and postoperatively for retinal sensitivity measurement. RESULTS: Totally ten patients (ten eyes) were included for analysis. The mean retinal sensitivity within central 12° and 40° was statistically improved after surgery (P < 0.05). The number of absolute or relative scotoma (stimulus values ≤4 dB) within central 4° showed a significant reduction postoperatively. There was also a significant increase in visual acuity postoperatively. CONCLUSION: Patients with large MH have a great successful rate by receiving inverted ILM flap technique. In our study, all MHs of ten eyes were closed postoperatively. The results also demonstrated that ILM flap technique improves both the functional and anatomic outcomes.

Multiple Single Nucleotide Polymorphism Testing Improves the Prediction of Diabetic Retinopathy Risk with Type 2 Diabetes Mellitus.

Diabetic retinopathy (DR) is one of the most frequent causes of irreversible blindness, thus prevention and early detection of DR is crucial. The purpose of this study is to identify genetic determinants of DR in individuals with type 2 diabetic mellitus (T2DM). A total of 551 T2DM patients (254 with DR, 297 without DR) were included in this cross-sectional research. Thirteen T2DM-related single nucleotide polymorphisms (SNPs) were utilized for constructing genetic risk prediction model. With logistic regression analysis, genetic variations of the FTO (rs8050136) and PSMD6 (rs831571) polymorphisms were independently associated with a higher risk of DR. The area under the curve (AUC) calculated on known nongenetic risk variables was 0.704. Based on the five SNPs with the highest odds ratio (OR), the combined nongenetic and genetic prediction model improved the AUC to 0.722. The discriminative accuracy of our 5-SNP combined risk prediction model increased in patients who had more severe microalbuminuria (AUC = 0.731) or poor glycemic control (AUC = 0.746). In conclusion, we found a novel association for increased risk of DR at two T2DM-associated genetic loci, FTO (rs8050136) and PSMD6 (rs831571). Our predictive risk model presents new insights in DR development, which may assist in enabling timely intervention in reducing blindness in diabetic patients.

Natural history and visual outcome of nonarteritic anterior ischemic optic neuropathy in Southern Taiwan: a pilot study.

PURPOSE: To investigate the natural course, visual outcome, and risk factors for visual loss after nonarteritic anterior ischemic optic neuropathy (NAION) attack in Chinese patients from a tertiary medical center in Southern Taiwan. METHODS: This is a longitudinal observational study that included sixty NAION patients, who were seen in our neuro-ophthalmology clinic from 2007 to 2016. Records of their ophthalmic history, medical history, best-corrected visual acuity (BCVA), visual field (VF) testing, and optical coherence tomography (OCT) were obtained for analysis. RESULTS: When the first visit was within two weeks after NAION onset, 62% of patients had BCVA of less than 0.1 (logMAR BCVA ≥ 1) and 38% had at least moderate-severe depression (VF grade ≥ 3) on VF on the initial visit. VA stabilized at three months after onset and was predictive of VA at 12 months. Diabetes mellitus was a risk factor associated with VA worsening. Sixty-one percent of patients had BCVA of less than 0.1 at 12 months after onset. VF remained relatively unchanged during the disease, with 41% eyes having VF grade ≥ 3 at 12 months after onset. On OCT, all quadrants of retinal nerve fiber layer thickened initially, returned to the level of the fellow eye at one month, and continued thinning up to 12 months slowly. CONCLUSION: In Southern Taiwan, a higher proportion of Chinese patients (over half) presented with severe visual loss during the first two weeks of NAION attack and at 12 months after the onset of NAION as compared to the findings previously reported in Caucasians. Understanding the natural course of NAION in Chinese patients may provide insights toward a possible therapeutic window for NAION treatments in this group of patients.

Patchy Scotoma Observed in Chorioretinal Patchy Atrophy of Myopic Macular Degeneration.

Purpose: To investigate the retinal sensitivity of highly myopic eyes with chorioretinal patchy atrophy (PA) using microperimetry. Methods: Fifty-two eyes of 32 patients with high myopia were prospectively included. Twenty-two eyes of 16 patients had PA lesions; eyes without PA were analyzed as controls. Testing points on microperimetry in eyes with PA were designated as 3 zones: zone 1 as the PA lesion including its borders; zone 2 including testing points adjoining PA; zone 3 including all other testing points. Results: In the PA group, the mean retinal sensitivity in zone 1 was 2.1 ± 2.8 dB, zone 2 = 8.3 ± 4.3 dB, and zone 3 = 9.4 ± 4.1 dB. Sensitivity in zone 1 was significantly reduced than zones 2 and 3 (P < 0.001). The mean retinal sensitivity in the PA group was lower than controls (6.5 ± 4.3 vs 13.9 ± 4.1 dB, P < 0.001), and combined zone 2 and 3 in the PA group also presented lower retinal sensitivity (8.8 ± 4.0 dB). Conclusions: Eyes with PA generate patchy scotoma in PA lesions and reduced retinal sensitivity in regions beyond atrophic lesion on microperimetry. The presence of PA may be an indicator to reflect both significantly anatomical and functional alterations on myopic macular degeneration.

Health impact assessment of PM2.5 from a planned coal-fired power plant in Taiwan.

PURPOSE: To investigate the impact of a planned coal-fired power plant (CFPPT) in Shenao on air quality and health at subnational levels in Taiwan. METHODS: We applied the Gaussian trajectory transfer-coefficient (GTx) model to estimate annual average PM2.5 (particulate matter with aerodynamic diameter less than 2.5 µm) increments in 19 Taiwanese cities and counties caused by CFPPT operation. A population health risk assessment was performed by incorporating evidence of the health effects of PM2.5 provided by prospective studies and estimating long-term PM2.5 exposure. Additionally, we considered ischemic heart disease, stroke, lung cancer, and chronic obstruct pulmonary disease as the primary outcomes. The population-attributable fraction was used to estimate the county-level mortality burden attributable to CFPPT-generated PM2.5 in 2025. RESULTS: The estimated annual PM2.5 increments ranged from 0.004 µg/m3 (Taitung County) to 0.28 µg/m3 (Hsinchu County) due to the Shenao CFPPT. The total and premature deaths attributable to PM2.5 from Shenao CFPPT operation in Taiwan during 2025-2040 would be 576 (95% confidence interval [CI]: 537-619) and 145 (95% CI: 136-155), respectively. Notably, we estimated 198 (95% CI: 169-234) deaths and 58 (95% CI: 51-66) premature deaths, respectively, in New Taipei City, which accounted for over a quarter of the total deaths. Overall, the mortality rate attributable to the Shenao CFPPT in Taiwan was 6 per 10,000. CONCLUSION: A scientific approach should be adopted for assessing the impacts of CFPPT operation on population health, which can serve as a valuable policymaking reference for the government.

Fixation behavior in macular dystrophy assessed by microperimetry.

PURPOSE: To investigate the fixation behavior in macular dystrophy using microperimetry. METHODS: This retrospective study included patients with macular dystrophy and unilateral macular pucker. Macular dystrophic eyes were compared based on fixation within or outside of the atrophic region. The normal fellow eyes in patients with unilateral macular pucker formed the control group. Clinical and demographic characteristics of age, sex, best-corrected visual acuity, spherical equivalent, and fixation behavior (which included foveal mean sensitivity (MS), fixation MS, MS improvement, stability, centrality, and eccentric distance of fixation) were analyzed. A total of 58 patients were recruited, comprising 29 eyes of 29 patients in the macular dystrophy group and 29 eyes of 29 patients in the control group. RESULTS: Compared to the control group, patients with macular dystrophy had significantly poorer visual acuity, foveal MS, fixation MS, stability, and centrality, and more eccentric preferred retinal locations (PRLs). In macular dystrophy, the PRLs were most common on the superior side (48.3%). Compared to fixation in the atrophic region, PRLs out of the atrophic lesion gained more MS (7.41 vs. 0.89 dB, p = 0.001), although with less stable fixation (10.0 vs. 47.4%, p = 0.044). By multivariate linear regression, eccentric distance was found to be significantly associated with MS improvement (p = 0.023). CONCLUSIONS: The commonest location of PRLs in macular dystrophy is anatomically superior to the lesion. The dystrophic eye can gain better sensitivity by using PRLs outside the atrophic area.

Factors associated with corneal epithelial defects after pars plana vitrectomy.

PURPOSE: To investigate the risk factors associated with corneal epithelial defects (CED) and delayed healing (exceeding 1 week) following pars plana vitrectomy (PPV). METHODS: This retrospective study enrolled patients who underwent PPV at a single center in Taiwan between 2011 and 2012. Medical records were reviewed, including demographic, underlying disease, surgical indication, operation parameters, and existence of CED. These data were statistically analyzed. All patients were evaluated during follow-ups at day 1 and week 1 after PPV. Patients with persistent CED 1 week after PPV were diagnosed with delayed healing. RESULTS: A total of 255 patients were included in the study, consisting of 139 men and 116 women, with a mean age of 56.9 years. PPV was performed under the indications of rhegmatogenous retinal detachment (RRD), diabetic retinopathy, or vitreoretinal interface disease. Out of 255 eyes, 59 developed CED 1 day after surgery (23.1%), and CED was associated with younger age, diabetes mellitus (DM), RRD, longer duration of surgery, and silicon oil use during surgery. Among them, seven patients (11.9%) demonstrated delayed healing, which was associated with a higher rate of DM (p = 0.085), compared to patients who healed within 1 week. CONCLUSION: Patients with RRD, longer duration of surgery, and DM may be at risk of developing CED after PPV. In addition, patients with DM demonstrated a higher incidence of delayed corneal healing.

Retinal Detachment Associated With Basketball-Related Eye Trauma.

PURPOSE: Basketball is a popular sport involving significant body contact, which may frequently result in ocular trauma. The aim of this study was to evaluate the characteristics and visual outcomes of retinal detachment associated with basketball-related injury. DESIGN: Retrospective, interventional case series. METHODS: We reviewed the course of patients who sustained traumatic retinal detachment from basketball-related ocular trauma between 2003 and 2015. RESULTS: Thirteen patients were evaluated for basketball-related traumatic retinal detachment. Twelve (92%) were male and 1 (8%) female, with an average age of 18.2 years. The majority (9 of 13, 70%) of patients had moderate-to-high myopia, and none were using protective eyewear when they sustained the eye trauma. Rhegmatogenous retinal detachment was observed in all eyes. The preoperative mean visual acuity was 20/625 (range, hand motions to 20/20). Initial surgery using scleral buckling alone was performed in most (8 of 13, 62%) of the patients. Retinal reattachment was achieved in 10 (76%) eyes after the first operation and in 12 (92%) at the end of the intervention. The mean follow-up was 3.9 years (range, 4 months to 12 years). The visual acuity during last follow-up was 20/231 (range, light perception to 20/20). In the multivariable analysis, initial visual acuity was an independent factor affecting the final visual outcome (P = .006). CONCLUSION: Retinal detachment associated with basketball-related injury may cause severe visual loss. In the current study, all retinal detachments were of rhegmatogenous type and commonly occurred in young individuals with myopia. Initial visual acuity was associated with the prognosis. Risk awareness for early detection and intervention are important in these traumas.

GORE-TEX VASCULAR GRAFT FOR MACULAR BUCKLING IN HIGH MYOPIA EYES.

PURPOSE: To evaluate a new application of an expanded polytetrafluoroethylene (Gore-Tex) vascular graft for use in macular buckling surgery for treatment of highly myopic eyes. METHODS: The Gore-Tex vascular graft was used as a macular buckling material in eight consecutive cases of myopic macular diseases which included fovea detachment, foveoschisis, or macular hole retinal detachment. RESULTS: Retinal reattachment was achieved in all cases except one which had partial resolution (88%). The postoperative best-corrected visual acuity ranged from 20/2000 to 20/100 depending on the degree preexisting macular degeneration, and significant better than the preoperative best-corrected visual acuity (P = 0.048, paired t-test). During the follow-up period, which ranged from 8 months to 3 years, no eye developed buckle-related complications such as infection or dislocation. CONCLUSION: The initial pilot results from this series using a Gore-Tex graft for macular buckling is promising. Throughout the follow-up period, the Gore-Tex was well tolerated in the highly myopic eyes. Large scale and long-term follow-up is warranted.

Isolates and antibiotic susceptibilities of endophthalmitis in postcataract surgery: a 12-year review of culture-proven cases.

The purpose of this study was to investigate the spectrum of organisms causing endophthalmitis after cataract surgery in a tertiary medical center in Taiwan and the antibiotic susceptibilities. This was a retrospective case series study. Patients with endophthalmitis after cataract surgery from January 2004 to July 2015 were reviewed. The outcome measures included the identification of isolates, antibiotic susceptibilities, and final visual outcomes. Twenty-one organisms were isolated from 19 cases. The most common organisms were Enterococcus in 38.1 %, especially Enterococcus faecalis, followed by Staphylococcus epidermidis in 28.6 % and Staphylococcus aureus in 9.5 %. All of the Gram-positive isolates tested were susceptible to vancomycin (100 %), and ceftazidime and amikacin were susceptible for Gram-negative organisms. The Gram-positive organisms remain to be the predominant cause of postoperative endophthalmitis, and Enterococcus species has had an increasing incidence. Vancomycin is still the most powerful antibiotic for Gram-positive organisms, while ceftazidime and amikacin are effective for Gram-negative bacteria.

Serum uric acid concentration is associated with worsening in severity of diabetic retinopathy among type 2 diabetic patients in Taiwan--a 3-year prospective study.

AIMS: To explore the role of serum uric acid (SUA) concentration in diabetic retinopathy (DR) for patients with type 2 diabetes mellitus (T2DM). METHODS: A 3-year prospective study in 749 patients with T2DM and without proliferative diabetic retinopathy (PDR) was conducted at a medical center. Baseline SUA concentration and parameters of glycemic control, blood pressure, kidney disease, and lipid profiles were analyzed to determine their contribution to DR. RESULTS: Fundus examination showed that 184 patients (24.6%) had non-proliferative retinopathy and 565 (75.4%) without DR at baseline. After 3 years, increase in the severity of DR was recognized in 103 patients (13.8%), including 81 patients with newly developed DR. Patients with increase in severity of DR positively associated with duration of DM (11.9 vs. 9.4 years, p = 0.001), HbA1c (7.6 vs. 7.2%, p = 0.001), albuminuria (45.5 vs. 31.0%, p = 0.006), and SUA (6.47 vs. 5.87 mg/dl, p<0.001) than did those without change in DR stage. Cox regression showed that patients with SUA in the 3rd (5.9-6.9 mg/dl) and 4th (≥ 7.0mg/dl) quartiles had hazard ratios for DR worsening of 2.57 and 3.66 (95% C.I. 1.30-5.08 and 1.92-7.00) when compared with patients with SUA in the 1st quartile (<4.9 mg/dl). CONCLUSIONS: SUA concentration is associated with the increase in severity of DR over a 3-year period in patients with T2DM. Further study is required to define the exact role of SUA in DR.

The regulation of DNA adsorption and release through chitosan multilayers.

To sustain transgene expression, chitosan was studied to immobilize DNA using layer-by-layer assembly to form polyelectrolyte multilayers (PEMs). Higher DNA concentrations and longer deposition periods demonstrated more DNA adsorptions to PEMs. By adjusting pH and the molecular weight of chitosan, PEM structures were manipulated. Chitosan molecules adsorption to PEMs increased when they were at pH 6 because of their low protonation. Furthermore, the configuration of chitosan favored a coiled-form when the pH was high, as the intramolecular repulsion decreased. Therefore, interdiffusion of polyelectrolytes in PEMs was promoted to increase DNA adsorption, especially for chitosan with high molecular weight. For the release experiments, because PEMs fabricated by lower pH chitosan owned less chitosan molecules, DNA release was enhanced. However, this phenomenon did not happen to chitosan with high molecular weight, which should be due to the entanglement between polymer chains. This comprehensive approach should be beneficial to substrate-mediated gene delivery applications.

Delivery of nucleic acids, proteins, and nanoparticles by arginine-rich cell-penetrating peptides in rotifers.

Cell-penetrating peptides (CPPs) are a group of short, membrane-permeable cationic peptides that represent a nonviral technology for delivering nanomaterials and macromolecules into live cells. In this study, two arginine-rich CPPs, HR9 and IR9, were found to be capable of entering rotifers. CPPs were able to efficiently deliver noncovalently associated with cargoes, including plasmid DNAs, red fluorescent proteins (RFPs), and semiconductor quantum dots, into rotifers. The functional reporter gene assay demonstrated that HR9-delivered plasmid DNAs containing the enhanced green fluorescent protein and RFP coding sequences could be actively expressed in rotifers. The 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay further confirmed that CPP-mediated cargo delivery was not toxic to rotifers. Thus, these two CPPs hold a great potential for the delivery of exogenous genes, proteins, and nanoparticles in rotifers.

Clinical implications of serous retinal detachment in branch retinal vein occlusion and response after primary intravitreal bevacizumab injection.

PURPOSE: To evaluate the impact of macular serous retinal detachment (SRD) and its relationship to treatment outcome after primary intravitreal bevacizumab (IVB) injection in patients with branch retinal vein occlusion (BRVO) and macular edema (ME). METHODS: Seventy-three patients with ME secondary to BRVO who received primary IVB (2.5 mg/0.1 mL) were included in this study. The specific ME patterns were investigated using optical coherence tomography (OCT) examination. Visual acuity (VA), central macular thickness (CMT), and macular volume at baseline; at 1, 3, and 6 months; and at final visit after primary IVB were retrospectively analyzed and compared between patients with and without SRD. RESULTS: SRD was found in 25 patients (34.2%). The baseline CMT was significantly thicker in patients with SRD than in those without it (648.4±200.5 µm vs. 440.3±119.6 µm, P<0.001). Six months after primary IVB injection, a greater reduction in CMT change from baseline was observed in the SRD group (412.5±227.2 µm) than in the group without SRD (118.5±175.2 µm) (P<0.001). The improvement of logarithm of the minimum angle of resolution VA was also greater in the SRD group than in the group without SRD (-0.64±0.52 and -0.28±0.62 respectively, P=0.015). Logistic regression analysis showed that the presence of SRD was an independent factor for visual improvement in BRVO (P=0.027). CONCLUSION: Patients with SRD had greater functional and morphological improvements at 6 months after primary IVB therapy. The results of this study suggest that the presence of SRD observed on OCT may be an indicator of favorable clinical response after IVB injections and that in BRVO patients with SRD, bevacizumab may be a good alternative for treatment.

A gene delivery system for insect cells mediated by arginine-rich cell-penetrating peptides.

Most bioactive macromolecules, such as protein, DNA and RNA, basically cannot permeate into cells freely from outside the plasma membrane. Cell-penetrating peptides (CPPs) are a group of short peptides that possess the ability to traverse the cell membrane and have been considered as candidates for mediating gene and drug delivery into living cells. In this study, we demonstrate that three arginine-rich CPPs (SR9, HR9 and PR9) are able to form stable complexes with plasmid DNA and deliver DNA into insect Sf9 cells in a noncovalent manner. The transferred plasmid DNA containing enhanced green fluorescent protein (EGFP) and red fluorescent protein (RFP) coding regions could be expressed in cells functionally assayed at both the protein and RNA levels. Furthermore, treatment of cells with CPPs and CPP/DNA complexes resulted in a viability of 84-93% indicating these CPPs are not cytotoxic. These results suggest that arginine-rich CPPs appear to be a promising tool for insect transgenesis.