Effectiveness and safety of injectable human papilloma virus vaccine administered as eyedrops.

Mucosal vaccines have the advantages of ease of administration and the induction of strong mucosal immunity and a systemic immune response. Recently, the eye mucosa has been shown to be an effective and safe alternative vaccination route against influenza, Toxoplasma gondii infection, and hemolytic uremic syndrome in mice. In this study, we showed that the commercially available human papilloma virus (HPV) vaccine, Cervarix, induced significant immune reactions in terms of anti-HPV antigen (Ag)-specific immunoglobulin G (IgG) and IgA antibody production following eyedrop (ED) vaccination in mice. The HPV ED vaccines (EDV) provoked no signs of inflammation within 24 h, as indicated by the inflammatory cytokine mRNA levels and infiltration of mononuclear cells in inoculation sites. Moreover, the morphology of the cornea and retina and intraocular pressure of mice did not change after the HPV EDV. The functions of photoreceptor cells, including rod and cone cells, were normal following the HPV EDV inoculation in mice. These results suggest that Cervarix EDV could be a potent, safe, and effective mucosal vaccine against HPV-associated cancers.

Synthesizing realistic high-resolution retina image by style-based generative adversarial network and its utilization.

Realistic image synthesis based on deep learning is an invaluable technique for developing high-performance computer aided diagnosis systems while protecting patient privacy. However, training a generative adversarial network (GAN) for image synthesis remains challenging because of the large amounts of data required for training various kinds of image features. This study aims to synthesize retinal images indistinguishable from real images and evaluate the efficacy of the synthesized images having a specific disease for augmenting class imbalanced datasets. The synthesized images were validated via image Turing tests, qualitative analysis by retinal specialists, and quantitative analyses on amounts and signal-to-noise ratios of vessels. The efficacy of synthesized images was verified by deep learning-based classification performance. Turing test shows that accuracy, sensitivity, and specificity of 54.0 ± 12.3%, 71.1 ± 18.8%, and 36.9 ± 25.5%, respectively. Here, sensitivity represents correctness to find real images among real datasets. Vessel amounts and average SNR comparisons show 0.43% and 1.5% difference between real and synthesized images. The classification performance after augmenting synthesized images outperforms every ratio of imbalanced real datasets. Our study shows the realistic retina images were successfully generated with insignificant differences between the real and synthesized images and shows great potential for practical applications.

Comparison of ophthalmic toxicity of light-emitting diode and organic light-emitting diode light sources.

The use of organic light-emitting diodes (OLEDs) has rapidly increased in recent years. However, the effect of OLEDs on human health has not been studied yet. We investigated morphologic and functional changes after OLEDs exposure of human ocular cells, including corneal, conjunctival, lens, and retinal pigment epithelial cells, and mouse eyes. In corneal and conjunctival epithelial cells, the levels of reactive oxygen species production and interleukin-8 expression after white light-emitting diodes (LED) exposure were significantly greater than those after OLED exposure. Although no gross morphologic changes of the eyelid or cornea were found in LED- or OLED-exposed mice, oxidative stress on ocular surface was significantly increased, and the outer nuclear layer (ONL) was significantly shorter in both light-treated groups than the control group. Moreover, ONL thickness was significantly lower in the LED group than the OLED group. The electroretinography response was significantly lower in light exposure group, and there was significant difference between LED- and OLED-treated mice. Although OLED exhibits certain ocular toxicity, it can be less toxic to eyes than LED. The higher blue-wavelength energy of LED light might be the reason for its higher toxicity relative to OLED.

Lacinutrix chionocetis sp. nov., isolated from gut of a red snow crab.

A Gram-negative, aerobic, non-motile, rod-shaped bacterial strain, designated MAB-07T, was isolated from the gut of a red snow crab. The novel strain grew optimally at 20 °C, pH 7.0-8.0, and in the presence of 3% (w/v) NaCl. A phylogenetic analysis based on the 16S rRNA gene sequence indicated that the strain MAB-07T belongs to the type strains of species of the genus Lacinutrix. Strain MAB-07T exhibited 16S rRNA gene sequence similarity values of 95.5-97.8% with the type strains of species of the genus Lacinutrix. The predominant cellular fatty acids of strain MAB-07T were iso-C15:1 G (27.5%) and iso-C15:0 (21.7%). The major respiratory quinine was identified as MK-6. The polar lipids consisted of phosphatidylethanolamine, four unidentified aminolipids, and two unidentified lipids. The genomic DNA G + C content was determined to be 33.3%, and its DNA-DNA relatedness values with the type strains of L. venerupis, L. mariniflava, L. jangbogonensis, L. algicola, and Olleya aquimaris were 28-32%. Based on the data from this polyphasic taxonomic study, strain MAB-07T is considered to represent a novel species of the genus Lacinutrix, for which the name L. chionocetis sp. nov. is proposed. The type strain is MAB-07T (=KCTC 42767T = JCM 30988T).

Inactivated Eyedrop Influenza Vaccine Adjuvanted with Poly(I:C) Is Safe and Effective for Inducing Protective Systemic and Mucosal Immunity.

The eye route has been evaluated as an efficient vaccine delivery routes. However, in order to induce sufficient antibody production with inactivated vaccine, testing of the safety and efficacy of the use of inactivated antigen plus adjuvant is needed. Here, we assessed various types of adjuvants in eyedrop as an anti-influenza serum and mucosal Ab production-enhancer in BALB/c mice. Among the adjuvants, poly (I:C) showed as much enhancement in antigen-specific serum IgG and mucosal IgA antibody production as cholera toxin (CT) after vaccinations with trivalent hemagglutinin-subunits or split H1N1 vaccine antigen in mice. Vaccination with split H1N1 eyedrop vaccine antigen plus poly(I:C) showed a similar or slightly lower efficacy in inducing antibody production than intranasal vaccination; the eyedrop vaccine-induced immunity was enough to protect mice from lethal homologous influenza A/California/04/09 (H1N1) virus challenge. Additionally, ocular inoculation with poly(I:C) plus vaccine antigen generated no signs of inflammation within 24 hours: no increases in the mRNA expression levels of inflammatory cytokines nor in the infiltration of mononuclear cells to administration sites. In contrast, CT administration induced increased expression of IL-6 cytokine mRNA and mononuclear cell infiltration in the conjunctiva within 24 hours of vaccination. Moreover, inoculated visualizing materials by eyedrop did not contaminate the surface of the olfactory bulb in mice; meanwhile, intranasally administered materials defiled the surface of the brain. On the basis of these findings, we propose that the use of eyedrop inactivated influenza vaccine plus poly(I:C) is a safe and effective mucosal vaccine strategy for inducing protective anti-influenza immunity.

The role of systemic immunomodulatory treatment and prognostic factors on chronic ocular complications in Stevens-Johnson syndrome.

PURPOSE: To compare the effect of early systemic immunomodulatory treatment and to identify prognostic factors of chronic ocular complications in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients. DESIGN: Retrospective, comparative, multicenter study. PARTICIPANTS: Forty-three patients admitted to 1 of 3 University Hospitals (Seoul National University Hospital, Chonnam National University Hospital, and Yonsei University Hospital) with a diagnosis of SJS or TEN who were followed up for at least 6 months in Korea. METHODS: Patients were divided into 5 groups according to systemic immunomodulatory treatment received: systemic steroids (S), intravenous immunoglobulin (IVIG), combined S plus IVIG, systemic pulse steroids (PS), and supportive care only (C). Best-corrected visual acuity (BCVA) and chronic ocular surface complications score (COCS; range, 0-15) at final follow-up were compared among the 5 groups. Prognostic factors at onset (age, gender, causative drugs, initial visual acuities, acute ocular involvement score [range, 0-3], acute systemic involvement score [range, 0-16], systemic steroid dose, IVIG dose, and amniotic membrane transplantation [AMT]) were analyzed to predict final BCVA or COCS using logistic regression or linear regression analysis. MAIN OUTCOME MEASURES: Best-corrected visual acuity and COCS at final follow-up. RESULTS: The mean age and follow-up period of the patients was 30.5±21.0 years and 29.1±30.4 months, respectively. The acute systemic involvement score in the IVIG, S plus IVIG, and PS groups was significantly higher than that in the S and C groups (P < 0.001). However, final BCVA and COCS were not significantly different between groups, even after statistical adjustment. High COCS (≥8 points) was associated with female gender (P = 0.012) and AMT at the acute stage (P = 0.040). High acute ocular and systemic involvement scores were associated with worse COCS (P < 0.001), and COCS showed good correlation with final BCVA (R(2) = 0.7101; P < 0.0001). CONCLUSIONS: There were no therapeutic benefits of systemic immunomodulatory treatments in final visual outcome and COCS in SJS and TEN patients. Female gender and acute ocular and systemic involvement scores may be prognostic factors predicting chronic ocular complications.

Long-term result of maintenance treatment with tacrolimus ointment in chronic ocular graft-versus-host disease.

PURPOSE: To investigate the efficacy and safety of long-term maintenance treatment with tacrolimus ointment in chronic ocular graft-vs-host disease (GVHD) with ocular surface inflammation. DESIGN: A retrospective interventional consecutive case series. METHOD: Long-term maintenance treatment (≥6 months) with topical 0.02% tacrolimus ointment was applied to patients with chronic ocular GVHD with ocular surface inflammation (at least grade 2 inflammatory score). We evaluated the inflammatory score, steroid score and steroid use period of total duration, and numbers of inflammatory aggravations before and after tacrolimus treatment. The clinical outcomes were assessed by symptom score, ocular surface staining, Schirmer I test, tear break-up time (TBUT), and classification of chronic GVHD conjunctivitis at the initial and final examinations. RESULTS: Thirteen patients (24 eyes) were treated with tacrolimus ointment for up to 20 months (average 12.2 months). The ocular surface inflammatory score decreased from 2.8 to 0.6 (P = .001) within 2-8 weeks after starting tacrolimus ointment treatment. The numbers of inflammatory aggravation and the need for steroid treatment also decreased after initiating tacrolimus treatment. At the final follow-up, all patients reported improvement in clinical outcomes, compared to initial findings. Except for blurred vision or mild burning sensation, there were no reported side effects. CONCLUSION: Considering the chronic course of GVHD, long-term maintenance treatment with tacrolimus ointment could be useful and safe to locally treat ocular surface inflammation in chronic ocular GVHD.

Thromboaspiration of arteriovenous hemodialysis graft thrombosis using Desilets-Hoffman sheath: single-center experience.

PURPOSE: The purpose of this study was to evaluate the feasibility, efficacy and safety of percutaneous thromboaspiration with a 7F Desilets-Hoffman sheath compared with previously established percutaneous mechanical thrombectomy techniques in occluded hemodialysis grafts. MATERIALS AND METHODS: One thousand three hundred five patients (767 women, 538 men; mean age, 61.04±13.09 years; mean graft age, 36.64±30.80 mo) with 2,531 episodes of hemodialysis graft thrombosis underwent percutaneous thromboaspiration with a 7F Desilets-Hoffman sheath using criss-cross or apex puncture technique. Technical success rate, procedure time, complications and patency rates were analyzed. RESULTS: Technical success was achieved in 2,426 of 2,531 procedures (95.9%). Average procedure time of the intervention was 42.87±22.77 minutes. Primary patency rate was 61.9% at 3 mo, 41.2% at 6 mo and 19.6% at 1 year. Major complications occurred in 4.1% of cases (23 graft outflow rupture; 68 arterial emboli; 1 arterial dissection; 3 symptomatic pulmonary embolism; 1 stent migration) and minor complications occurred in 7.7% of cases (196 cases). These results were comparable to previously reported mechanical thrombectomy techniques in occluded hemodialysis grafts. CONCLUSIONS: Percutaneous thromboaspiration of occluded hemodialysis grafts with a Desilets-Hoffman Sheath is an effective and safe method.

Effect of voriconazole and ultraviolet-A combination therapy compared to voriconazole single treatment on Fusarium solani fungal keratitis.

PURPOSE: To demonstrate that ultraviolet-A (UV-A) and voriconazole combination therapy is more effective than voriconazole single treatment for fungal keratitis. METHODS: The in vitro UV-A (375 nm) fungicidal effect was evaluated on Fusarium solani solutions. Each fungal solution was irradiated with different UV-A irradiation doses. Also, a fungal solution containing voriconazole was also irradiated with UV-A. The in vivo therapeutic effect of UV-A and voriconazole treatment was studied in a rabbit keratitis model. Fungi were injected intrastromally into the cornea of 16 rabbits. Each treatment was initiated 3 days after fungal injection and continued up to 8 days for the following groups: Group 1, control; Group 2, treated with UV-A once a day; Group 3, treated with voriconazole 3 times a day; Group 4, treated with voriconazole 3 times a day and UV-A once a day. On the last day, the sclera-cornea buttons were extracted and microbiological and histological evaluations were performed. RESULTS: The colony-forming units (CFUs) of fungal solutions in culture significantly decreased with UV-A irradiation. The CFUs of fungal solutions containing voriconazole also decreased with UV-A irradiation. In vivo, clinical scores of Group 3 (P=0.03) and Group 4 (P=0.02) 5 days after treatment were significantly lower compared to that of Group 1. The clinical score of Group 4 (P=0.03) 5 days after treatment was significantly lower compared to that of Group 3. The histopathological scores 5 days after treatment were significantly lower in Group 4 compared to those of Group 1 (P<0.01) and Group 3 (P=0.02). Based on our CFU analysis, only Group 4 showed significantly lower CFUs compared to Group 1 (P=0.04). CONCLUSIONS: UV-A and voriconazole combination treatment could be a safe and effective alternative to voriconazole single treatment for fungal keratitis.

Evaluation of dry eye and meibomian gland dysfunction after cataract surgery.

PURPOSE: To evaluate dry eye and meibomian gland dysfunction after cataract surgery. DESIGN: Prospective observational case series. METHODS: We studied 58 eyes of 48 patients who underwent phacoemulsification and evaluated them preoperatively and at 1 month and 3 months postoperatively. Ocular symptom scores, lid margin abnormalities, superficial punctate keratopathies (SPKs), tear film break-up time (TBUT), Schirmer test, lower tear meniscus height, depth, and area using Fourier domain optical coherence tomography, meibum expressibility and images of the meibomian glands using meibography were measured. RESULTS: The ocular symptom scores were worse at 1 month and 3 months postoperatively (P < 0.001 and P < 0.001, respectively). Lid margin abnormalities were significantly increased (P < 0.001 and P < 0.001, respectively) and TBUT decreased postoperatively (P < 0.001 and P < 0.001, respectively). Meibum expressibility decreased at 3 months postoperatively (P = 0.016); however, meibography score, SPK, lower tear meniscus height, depth and area and the Schirmer test did not change significantly postoperatively (all P values >0.05). CONCLUSION: Meibomian gland function may be altered without accompanying structural changes after cataract surgery.

Conjunctival mini-flap operation for restrictive strabismus after periocular surgery.

PURPOSE: To investigate the effect of conjunctival mini-flap operation to treat restrictive strabismus in patients with diplopia caused by conjunctival adhesion and hyperplasia after periocular surgery. DESIGN: Case series study. METHODS: Eleven patients with diplopia and restrictive strabismus attributable to conjunctival dysplasia after periocular surgery underwent a conjunctival mini-flap surgery without a muscle operation and were followed-up at 1, 3, and 6 months after surgery. The Hess screen test, binocular single vision field with Goldmann perimetry, and extraocular muscle movement were analyzed pre- and post-operatively. Patient satisfaction with the cosmetic results of conjunctival mini-flap operation was also investigated. RESULTS: The mean preoperative alignment deviation in primary position was 10.4 ± 5.6 prism diopters (PD). Diplopia in the primary position was resolved in 95% of the patients. The mean postoperative deviation was 1.36 ± 2.34 PD at the primary position. No significant complications or recurrences were noted after mean 9.5 ± 4.2 months follow-up. CONCLUSION: Conjunctival mini-flap operation is an effective and safe surgical technique for treating patients with diplopia and restrictive strabismus following periocular surgery.

Analysis of tear cytokines and clinical correlations in Sjögren syndrome dry eye patients and non-Sjögren syndrome dry eye patients.

PURPOSE: To compare concentrations of tear cytokines in 3 groups composed of Sjögren syndrome (SS) dry eye, non-Sjögren syndrome (non-SS) dry eye, and normal subjects. Correlations between ocular surface parameters and tear cytokines were also investigated. DESIGN: Prospective cross-sectional study. METHODS: SS dry eye patients (n = 24; 40 eyes) were diagnosed with primary SS according to the criteria set by the American-European Consensus Group. Non-SS dry eye patients (n = 25; 40 eyes) and normal subjects (n = 21; 35 eyes) were also enrolled. Tear concentrations of interleukin (IL)-17, IL-6, IL-10, IL-4, IL-2, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) were measured by a multiplex immunobead assay. Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), Schirmer I test, and fluorescein staining scores were obtained from dry eye patients. RESULTS: All cytokine levels except for IL-2 were highest in the SS group, followed by non-SS dry eye group and control subjects. Concentrations of IL-17, TNF-α, and IL-6 were significantly different among the 3 groups (IL-17: SS > control P < .001, non-SS > control P = .042, SS > non-SS P < .001; TNF-α: SS > control P = .006, non-SS > control P = .034, SS > non-SS P = .029; IL-6: SS > control P = .002, non-SS > control P = .032, SS > non-SS P = .002). IL-17 was significantly correlated with TBUT (R = -0.22, P = .012) and Schirmer I test (R = -0.36, P = .027) scores in the SS group. IL-6 was significantly correlated only with TBUT (R = -0.38, P = .02) in the non-SS group. CONCLUSIONS: Differences in tear cytokine levels and correlation patterns between SS dry eye and non-SS dry eye patients suggest the involvement of different inflammatory processes as causes of dry eye syndrome.

Fogarty balloon application technique in dislodging residual thrombus on the single sheath entry point at the apex of thrombosed loop grafts.

PURPOSE: We aimed to evaluate the effectiveness of the Fogarty balloon application in dislodging residual thrombus at the sheath entry point in a graft by using single apex puncture to declot thrombosed hemodialysis loop grafts. MATERIALS AND METHODS: The apex puncture technique was used in 520 cases to declot 376 hemodialysis loop grafts (male/female, 150/226; mean age, 58 years). The Fogarty balloon application technique, which uses the Fogarty balloon to the apex, was used to compress or displace the sheath entry point residual thrombus that did not wash away spontaneously by arterial . The frequency of the use of the technique, technical success, complications, and primary patency were evaluated. RESULTS: Sheath entry point thrombi were washed away spontaneously in 281 of 520 procedures (54%), and 184 procedures (35.4%) underwent a Fogarty balloon application. For a variety of reasons, the Fogarty balloon application technique was not performed in the remaining 55 procedures (10.6%). The technique was successful in 171 of 184 procedures (92.9%), and failed in 13 procedures, which required additional sheath insertion for the removal of sheath entry point thrombus. Complications included sheath dislodgment from the apex during Fogarty ballooning in one procedure and puncture site bleeding in one procedure. Primary patency was 60%, 35.2%, and 15.3% at 3, 6, and 12 months postprocedure, respectively. CONCLUSION: The Fogarty balloon application technique is safe and useful for the removal of residual thrombus at the apical, peri-sheath zone when declotting occluded hemodialysis loop grafts.

Morphometric changes in the cultured starry flounder, Platichthys stellatus, in open marine ranching areas.

Hatchery seeds released into open coasts for wildstock enhancement are often a biological pollutant and affect the recipient ecosystem integrity. We studied morphological changes in two hatchery populations of the starry flounder Platichthys stellatus; one released into the open coast from the hatchery (released population) and the other kept in the hatchery (captive population). The released population differed significantly from the captive population 3-36 months after release from the hatchery. Two-way ANOVA comparison revealed that 11 of 15 starry flounders differed significantly in morphological measurements, 10 of 15 differed in pigmentation, and 5 of 15 differed in morphometric ratios between the two populations. Pigmentation on the blind side (a representative sign of captive flounders) also differed between the two populations with an occurrence rate of 22.7% for the former and 39.5% for the latter groups. The released population was more similar to wild populations than to captive populations in terms of morphology; namely, longer and broader heads, a narrower body shape, longer fins, and a shorter and narrower peduncle.

Metastatic renal cell carcinoma to the orbit and the ethmoid sinus.

The orbit is an unusual site for metastatic renal cell carcinoma (RCC), and concurrent metastases of RCC to the ethmoid sinus and the orbit occur very rarely. The treatment goal of orbital and paranasal metastatic RCC is total exenteration. We report a rare case of metastatic RCC to the orbit and the ethmoid sinus. The patient underwent total exenteration, craniotomy, and total maxillectomy. Six years after surgery, the patient showed no sign of metastasis and had successful cosmetic result by using orbital prosthesis.

Two Cases of Laparoscopic Adhesiolysis for Chronic Abdominal Pain without Intestinal Obstruction after Total Gastrectomy.

Chronic abdominal pain remains a challenge to all known diagnostic and treatment methods with patients undergoing numerous diagnostic work-ups including surgery. However, the surgical treatment of patients with chronic intractable abdominal pain is controversial. There has been no discussion of the indications for adhesiolysis in cases of obstruction or strangulation of the bowel, and adhesiolysis by laparotomy has never gained acceptance as a treatment modality for chronic abdominal pain. One of the reasons for this lack of acceptance is the high complication rate during and after adhesiolysis. Laparoscopic surgery has been accepted as a technique for diagnostic and therapeutic procedures in general surgery. Laparoscopy allows surgeons to see and treat many abdominal changes that could not otherwise be diagnosed. Here we report two cases of successful symptomatic improvement through laparoscopic adhesiolysis for chronic abdominal pain without intestinal obstruction after total gastrectomy.

Presumed sclerotomy site bleeding inflowing into the anterior chamber after the removal of a 23-gauge microcannula in 23-gauge sutureless vitrectomy.

We experienced two cases of the influx of the sclerotomy site bleeding into the anterior chamber during 23-gauge sutureless vitrectomy for pseudophakic rhegmatogenous retinal detachment. Soon after the removal of a 23-gauge microcannula at the end of the surgery, presumed sclerotomy site hemorrhage was rapidly fluxed into the anterior chamber. The anterior chamber bleeding might come from the sclerotomies rather than from episcleral vessels. The posterior pressure in the gas-filled pseudophakic eye might have pushed the sclerotomy site bleeding into the anterior chamber. We could not find any vitreous hemorrhages. The hemorrhage within the anterior chamber spontaneously absorbed within 14 days.

Cataract and refractive surgery in ; a survey of KSCRS members from 1995~2006.

PURPOSE: This purpose of this report was to study trends in cataract and refractive surgeries conducted during the past twelve years and to compare results to previous reports from the ASCRS and New Zealand (NZ) in order to forecast future medical services. METHODS: We surveyed members of the Korean Society of Cataract and Refractive Surgery (KSCRS) every year from 1995 to 2006, and studied changes in cataract and refractive surgeries (RS). RESULTS: The duration of hospitalization has been gradually decreasing to the point that a one day hospitalization following surgery has become common. The rate of topical anesthesia use has significantly increased since 1998. Sutureless incision methods are now commonly practiced. The use of acryl IOL as an optic material has been gradually increasing for cataract surgeries. KSCRS members showed an interest in the special intraocular lenses as multifocal IOL. While Excimer laser PRK was the most popular refractive surgery during the first stage, KSCRS members increasingly prefer LASIK to the Excimer laser PRK. Regression of the corrected visual acuity, dry eye, night halo, and flashes were the most common complications following refractive surgeries. Medical disputes related to PRK and LASIK have been gradually increasing throughout the study period. CONCLUSIONS: We confirm that the KSCRS practice styles for cataract and RS are similar to those of the ASCRS and NZ. We infer a world-wide trend from the comparison of these three societies.