Interactions between Malassezia and New Therapeutic Agents in Atopic Dermatitis Affecting Skin Barrier and Inflammation in Recombinant Human Epidermis Model.

Several studies have reported the pathogenic role of Malassezia in atopic dermatitis (AD); the significance of Malassezia's influence on AD needs to be further investigated. Dupilumab, a monoclonal antibody to anti-Interleukin (IL) 4Rα, and ruxolitinib, a Janus kinase (JAK)1/2 inhibitor, are the first approved biologics and inhibitors widely used for AD treatment. In this study, we aimed to investigate how Malassezia Restricta (M. restricta) affects the skin barrier and inflammation in AD and interacts with the AD therapeutic agents ruxolitinib and anti-IL4Rα. To induce an in vitro AD model, a reconstructed human epidermis (RHE) was treated with IL-4 and IL-13. M. restricta was inoculated on the surface of RHE, and anti-IL4Rα or ruxolitinib was supplemented to model treated AD lesions. Histological and molecular analyses were performed. Skin barrier and ceramide-related molecules were downregulated by M. restricta and reverted by anti-IL4Rα and ruxolitinib. Antimicrobial peptides, VEGF, Th2-related, and JAK/STAT pathway molecules were upregulated by M. restricta and suppressed by anti-IL4Rα and ruxolitinib. These findings show that M. restricta aggravated skin barrier function and Th2 inflammation and decreased the efficacy of anti-IL4Rα and ruxolitinib.

Ex Vivo Treatment with Allogenic Mesenchymal Stem Cells of a Healthy Donor on Peripheral Blood Mononuclear Cells of Patients with Severe Alopecia Areata: Targeting Dysregulated T Cells and the Acquisition of Immunotolerance.

Alopecia areata (AA) is an autoimmune condition related to the collapse of the immune privilege of hair follicles. Certain AA populations present severe clinical manifestations, such as total scalp hair or body hair loss and a treatment refractory property. The aim of this study was to assess the effects of allogenic human mesenchymal stem cells (hMSCs) from healthy donors on the peripheral blood mononuclear cells (PBMCs) of severe AA patients, with a focus on the change in the cell fraction of Th1, Th17, and Treg cells and immunomodulatory functions. PBMCs of 10 AA patients and eight healthy controls were collected. Levels of Th17, Th1, and Treg subsets were determined via flow cytometry at baseline, activation status, and after co-culturing with hMSCs. All participants were severe AA patients with SALT > 50 and with a long disease duration. While the baseline Th1 and Treg levels of AA patients were comparable to those of healthy controls, their Th17 levels were significantly lower than those of the controls. When stimulated, the levels of CD4+IFN-γ+ T cells of the AA patients rose sharply compared to the baseline, which was not the case in those of healthy controls. The cell fraction of CD4+Foxp3+ regulatory T cells also abruptly increased in AA patients only. Co-culturing with allogenic hMSCs in activated AA PBMCs slightly suppressed the activation levels of CD4+INF-γ+ T cells, whereas it significantly induced the differentiation of CD4+Foxp3+ regulatory T cells. However, these changes were not prominent in the PBMCs of health controls. To examine the pathomechanisms, PBMCs of healthy donors were treated with IFN-γ to induce AA-like environment and then treated with allogenic grants and compared with ruxolitinib as a positive treatment control. hMSC treatment was shown to significantly inhibit the mRNA levels of proinflammatory cytokines, such as IFN-γ, TNF-α, IL-1α, IL-2R, IL-15, and IL-18, and chemokines, such as CCR7 and CCR10, in IFN-treated PBMCs. Interestingly, hMSCs suppressed the activation of JAK/STAT signaling by IFN in PBMCs with an effect that was comparable to that of ruxolitinib. Furthermore, the hMSC treatment showed stronger efficacy in inducing Foxp3, IL-10, and TGF-ß mRNA transcription than ruxolitinib in IFN-treated PBMCs. This study suggests that allogenic hMSC treatments have therapeutic potential to induce immune tolerance and anti-inflammatory effects in severe AA patients.

Preventive Effects of a Human Hematopoietic Mesenchymal Stem Cell (hHMSC) Therapy in Ovalbumin-Induced Food Allergy.

No effective therapeutic strategies have been developed against food allergies. Immunomodulation during early infant period could prevent the development of food allergies. We investigated the preventive effects of human hematopoietic mesenchymal stem cells (hHMSCs) in mice with ovalbumin (OVA)-induced food allergy. BALB/c mice with OVA-induced food allergy were divided into 3 groups, and each group was treated with hHMSCs or hHMSC culture medium (hHMSC-CM) or saline. Ear thickness, allergy score, rectal temperature, and diarrhea occurrence were checked. Total IgE, OVA-specific IgE, and mucosal mast cell protease-1 (mMCP-1) were measured by ELISA. Other allergic parameters were analyzed using histology specimens, RT-PCR, and flow cytometry. Treatment with hHMSCs or hHMSC-CM significantly suppressed the frequency of anaphylactic response and rectal temperature decline, reduced diarrhea, total IgE, OVA-specific IgE, and mMCP-1. While the treatment decreased the level of Th2 cytokines, it enhanced IL-10 and TGF-ß1 mRNA. Exposure to hHMSC or hHMSC-CM did not generate regulatory T cells, but reduced mast cells. The immunomodulatory effect on the Th2 cytokines was greater in hHMSC-CM than in hHMSCs. hHMSC treatment may be a promising preventive intervention against food allergy. Further studies are needed to elucidate the key substances released from hHMSC to induce immune tolerance.

Mesenchymal Stem Cells Antagonize IFN-Induced Proinflammatory Changes and Growth Inhibition Effects via Wnt/ß-Catenin and JAK/STAT Pathway in Human Outer Root Sheath Cells and Hair Follicles.

Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. In this study, we aimed to examine the influence of human hematopoietic mesenchymal stem cells (hHMSCs) in the hORSCs in vitro model of AA and determine the mechanisms controlling efficacy. Interferon-gamma (IFN-γ) pretreatment was used to induce an in vitro model of AA in hORSCs. The effect of MSCT on the viability and migration of hORSCs was examined using co-cultures, the MTT assay, and migration assays. We investigated the expression of molecules related to the Wnt/ß-catenin pathway, JAK/STAT pathway, and growth factors in hHMSC-treated hORSCs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. hHMSCs increased hORSC viability and migration when they were co-cultured. hHMSCs reverted IFN-γ-induced expression-including NLRP3, ASC, caspase-1, CXCL-9 through 11, IL-1ß, and IL-15-and upregulated several growth factors and hair stem cell markers. hHMSCs activated several molecules in the Wnt/ß-catenin signaling pathway, such as in the Wnt families, ß-catenin, phosphorylated GSK-3ß and cyclin D1, and suppressed the expression of DKK1 induced by IFN-γ in hORSCs. hHMSCs suppressed the phosphorylation of JAK1 to 3, STAT1, and STAT3 compared to the controls and IFN-γ-pretreated hORSCs. These results demonstrate that hHMSCs increased hORSC viability and migration in the in vitro AA model. Additionally, MSCT definitely stimulated anagen survival and hair growth in an HF organ culture model. MSCT appeared to be associated with the Wnt/ß-catenin and JAK/STAT pathways in hORSCs.

Inflammasome-mediated Inflammation by Malassezia in human keratinocytes: A comparative analysis with different strains.

Malassezia species are associated with several common dermatologic conditions including pityriasis versicolor, seborrhoeic dermatitis, folliculitis, and atopic dermatitis and dandruff. However, its causal role remains to be established. We intended to explore the role of inflammasome activation in human keratinocytes in response to three different Malassezia species. We compared the different activation patterns of inflammasomes and the expression of pro-inflammatory cytokines and antimicrobial peptides by three different Malassezia species-M. restricta, M. globosa and M. sympodialis-in human keratinocytes. We found that different Malassezia species, especially M. restricta and M. globosa could induce nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin-domain-containing protein (NLRP)3-apoptosis-associated speck-like protein containing CARD (ASC) inflammasome activation and subsequent interleukin (IL)-1ß secretion in human keratinocytes. Malassezia species variably induced thymic stromal lymphopoietin, ß-defensin 2, and LL-37. IL-8 mRNA and IL-22 protein significantly increased in the M. sympodialis-treated group, and Chemokine C-C motif ligand (CCL)17 and CCL22 mRNA were increased in response to M. globosa- and M. restricta- treated keratinocytes, respectively. Our data show that various species of Malassezia promote variable inflammatory responses in keratinocytes by activating NLRP3 inflammasomes, pro-inflammatory cytokines and chemokines, and antimicrobial peptides.

Contribution of Autophagy-Notch1-Mediated NLRP3 Inflammasome Activation to Chronic Inflammation and Fibrosis in Keloid Fibroblasts.

Keloid is a representative chronic fibroproliferative condition that occurs after tissue injury. Emerging evidence showed that activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in the pro-inflammatory response in injured tissues. However, the role of NLRP3 inflammasome in keloid progression remains unclear. Notch signaling, which activates NLRP3 inflammasome, is known to contribute to scar formation in keloid, but the cause of enhanced Notch signaling in keloid is not clear. We sought to investigate whether autophagy regulates Notch1 signaling in keloid fibroblasts and determine whether Notch1 signaling might regulate NLRP3 inflammasomes and myofibroblast differentiation. An in vitro model of keloid was established by culturing primary keloid fibroblasts from patients. Expression levels of Notch1, NLRP3 inflammasome proteins, pro-inflammatory cytokines, and myofibroblast markers in keloid fibroblasts were examined and compared with those in normal fibroblasts. Autophagy known to mediate Notch1 degradation was also monitored in fibroblasts. Small interfering RNA (siRNA) targeting Notch1 was used to transfect keloid fibroblasts to further examine the role of Notch signaling in NLRP3 inflammasome activation. Expression levels of Notch1 and NLRP3 inflammasome in keloid fibroblasts increased compared to those in normal fibroblasts. Such increases were accompanied by increased LC3 levels and reduced autophagic flux. Notch1 silencing in keloid fibroblasts by siRNA transfection significantly suppressed increased levels of overall NLRP3 inflammasome complex proteins, NF-kB, and α-smooth muscle actin. Autophagy induction by rapamycin treatment in keloid fibroblasts effectively suppressed expression levels of Notch1 and NLRP3 inflammasome proteins. Decreased autophagy activity in keloid can result in Notch1-mediated myofibroblast activation and NLRP3 inflammasome signaling activation which is critical for chronic inflammation. Collectively, these results identify Notch1 as a novel activator of NLRP3 inflammasome signaling leading to chronic tissue damage and myofibroblast differentiation in keloid progression.

Measuring the differences in work ratios between pediatric and adult ophthalmologic examinations.

PURPOSE: To assess the differences in work needed for pediatric and adult ophthalmologic examinations. METHODS: Seven ophthalmology residents conducted slit-lamp and refraction examinations on children 3-7 years of age and adults 20-69 years of age. The examiners reported the magnitude estimate (ME) of their work in relation to two references (cross-reference ME): average adult examination and average pediatric examination. The examination time was also measured. RESULTS: For the slit-lamp examination, 50 children and 58 adults were recruited. The ME was 1.45 (95% CI, 1.30-1.62) times higher for the pediatric examinations than for the adult examinations when the reference was an average adult case. With respect to time, the pediatric examinations took 1.22 (95% CI, 1.06-1.41) times longer than the adult examinations. For the refraction examinations, 58 children and 96 adults were recruited. The ME was 1.35 (95% CI, 1.21-1.52) times higher for the pediatric examinations. The pediatric examination took 1.32 (95% CI, 1.16-1.50) times longer than the adult examination. The cross-reference ME ratios measuring the pediatric over adult examinations against both the pediatric and adult reference cases were equivalent in both the slit-lamp and the refraction examinations; however, the ME and time ratios of the pediatric over the adult examinations were not equivalent for the slit-lamp or for the refraction examinations. CONCLUSIONS: The cross-reference ME showed that pediatric ophthalmologic examinations require more work than the adult examination with validity and reliability. The time estimate was insufficient as a single indicator for work estimation.

Prevalence and Factors Associated with the Use of Eye Care Services in South Korea: Korea National Health and Nutrition Examination Survey 2010-2012.

PURPOSE: To estimate the factors and prevalence of eye care service utilization in the South Korean population. METHODS: This cross-sectional, population-based study included data from 22,550 Koreans aged ≥5 years who participated in the Korea National Health and Nutrition Examination Survey from 2010 to 2012. For people aged 5 to 11 years (young children), information was based on self-reports of contact with eye care service in the past year; for people aged ≥12 years (older population), the information was based on the self-reported lifetime contact with eye care service. Univariate and multivariate logistic regression analyses of the complex sample survey data were performed. RESULTS: The prevalence of eye care service use in young children during the past year was 61.1% (95% confidence interval, 58.1%-64.1%), while that in the older population during their lifetime was 73.5%. Subjects aged 7 to 11 years were more likely to have had an eye examination in the past year than subjects aged 5 to 6 years (odds ratio, 3.83; 95% confidence interval, 2.37-6.19). Multivariate logistic regression analysis indicated that higher monthly household income, being a National Health Insurance holder, and having private health insurance were related to more frequent use of eye care services in young children. For the older population and women, those living in an urban area and those with a best-corrected visual acuity less than 20 / 40 in the worse-seeing eye were more likely to have had an eye examination during their lifetime. Low education level was associated with low lifetime use of eye care services in the older population. CONCLUSIONS: There are sociodemographic disparities with use of eye care services in South Korea. This population-based study provides information that is useful for determining different intervention programs based on sociodemographic disparities to promote eye care service utilization in South Korea.

Vision Improvement with Refractive Correction Does Not Completely Exclude Major Eye Diseases: Analyses of Visually Impaired South Korean Population in the Korea National Health and Nutrition Examination Survey 2009-2011.

PURPOSE: To investigate the association between vision improvement with refractive correction in the visually impaired eyes and the prevalence of ocular comorbidities in the South Korean population. MATERIALS AND METHODS: The data of 24,620 individuals in the Korea National Health and Nutrition Examination Survey (KNHANES 2009-2011) were reviewed. Visual impairment was defined as a presenting visual acuity < 20/60. The participants with visual impairment in at least one eye were divided into 3 groups according to the best-corrected visual acuity (group 1: <20/30, group 2: ≥20/30 but <20/25, and group 3: ≥20/25). The prevalence of ocular comorbidities was estimated and compared between the three groups. RESULTS: Visual impairment in at least one eye was found in 3031 individuals. Groups 1, 2, and 3 comprised 23.5%, 22.2%, and 54.3% of these visually impaired eyes, respectively. The prevalence of cataract, diabetic retinopathy, age-related macular degeneration, corneal opacity, blepharoptosis, and pterygium was similar to or even higher in group 2 compared to group 1. The prevalence of glaucoma and age-related macular degeneration was 5.40% and 11.39%, respectively, in group 2 and 3.31% and 3.76%, respectively, in group 3. CONCLUSIONS: Appropriate ophthalmologic examination is necessary even if people exhibit vision improvement after optical correction.

Longitudinal Changes in Refractive Error in a Pediatric Referral Population in Korea.

PURPOSE: To investigate changes in the spherical equivalent (SE) refractive error and astigmatism in a pediatric referral population in Korea with longitudinal follow-up and to evaluate the effect of risk factors on changes in refractive error. METHODS: This was a retrospective case series. In total, 221 patients who presented to a tertiary care hospital when aged 3 to 9 years and who underwent at least 10 years of follow-up were enrolled. The patients were divided into groups in terms of the initial extent of SE refractive error, the initial extent of astigmatism, sex, and ocular alignment. Changes in SE and astigmatism were compared among the groups. RESULTS: The patients were followed up for a mean of 11.19 ± 1.81 years. An overall negative shift in SE refractive error and increasing tendency in astigmatism during the follow-up period were noted. The negative shift in SE refractive error in the myopia group was significantly greater than those in the emmetropia and hyperopia groups. The change in astigmatism in the myopia group was significantly greater than that in the hyperopia group. The change in astigmatism in the low astigmatism group was significantly greater than those in the moderate and high astigmatism groups. Sex did not influence the changes in SE refractive error or astigmatism. CONCLUSIONS: A pediatric referral population in Korea showed a negative shift in SE refractive error and increasing tendency in astigmatism during childhood. Changes in refractive error may be influenced by the initial degree of SE refractive error and astigmatism. [J Pediatr Ophthalmol Strabismus. 2017;54(1):43-51.].

A nationwide population-based study of low vision and blindness in South Korea.

PURPOSE: To investigate the prevalence and associated risk factors of low vision and blindness in the Korean population. METHODS: This cross-sectional, population-based study examined the ophthalmologic data of 22,135 Koreans aged ≥5 years from the fifth Korea National Health and Nutrition Examination Survey (KNHANES V, 2010-2012). According to the World Health Organization criteria, blindness was defined as visual acuity (VA) less than 20/400 in the better-seeing eye, and low vision as VA of 20/60 or worse but 20/400 or better in the better-seeing eye. The prevalence rates were calculated from either presenting VA (PVA) or best-corrected VA (BCVA). Multivariate regression analysis was conducted for adults aged ≥20 years. RESULTS: The overall prevalence rates of PVA-defined low vision and blindness were 4.98% and 0.26%, respectively, and those of BCVA-defined low vision and blindness were 0.46% and 0.05%, respectively. Prevalence increased rapidly above the age of 70 years. For subjects aged ≥70 years, the population-weighted prevalence rates of low vision, based on PVA and BCVA, were 12.85% and 3.87%, respectively, and the corresponding rates of blindness were 0.49% and 0.42%, respectively. The presenting vision problems were significantly associated with age (younger adults or elderly subjects), female sex, low educational level, and lowest household income, whereas the best-corrected vision problems were associated with age ≥ 70 years, a low educational level, and rural residence. CONCLUSIONS: This population-based study provides useful information for planning optimal public eye health care services in South Korea.

Superamphiphilic Janus fabric.

Janus fabrics with superamphiphilicity were fabricated via electrospinning of polyacrylonitrile (PAN). PAN nanofibrous mats were formed on an aluminum foil substrate and then thermally treated to cause hydrolysis. An identical PAN solution was subsequently electrospun onto the hydrolyzed PAN layer, followed by peeling off of the bicomposite film from the collector substrate to produce a free-standing Janus fabric. On one side, the electrospun PAN mat exhibited superhydrophobic properties, with a water contact angle of 151.2°, whereas the initially superhydrophobic PAN sheet on the opposite side of the fabric was converted to a superhydrophilic surface (water contact angle of 0°) through hydrolysis of the surface functional groups induced by the thermal treatment. The resulting Janus fabrics exhibited both superhydrophobicity, repelling water on the one side, and superhydrophilicity, absorbing water on the other side. The organic solvent resistance of the PAN nanofibrous sheets was remarkably improved by incorporation of a tetraethyl orthosilicate. This facile and simple technique introduces a new route for the design and development of functional smart, robust fabrics from an inexpensive, commercially available polymer.

Robust superhydrophobic mats based on electrospun crystalline nanofibers combined with a silane precursor.

We demonstrate the fabrication of solvent-resistant, mechanically robust, superhydrophobic nanofibrous mats by electrospinning of poly(vinylidene fluoride) (PVDF) in the presence of inorganic silane materials. The solvent resistance and mechanical strength of nanofibrous mats were dramatically increased through the crystallization of as-spun PVDF fibers or incorporation of a tetraethyl orthosilicate (TEOS) sol into the nanofibrous matrix. The electrospun nanofibrous mats yielded a water contact angle of 156 degrees that did not vary with TEOS content. The solvent resistance and mechanical robustness of the electrospun mats were significantly enhanced through extensive cross-linking of TEOS, even after short PVDF annealing times. The interpenetrating polymer network, which embeds polymer chains in a TEOS network, allows the fabrication of robust functional nanofibers by combining semicrystalline polymers with electrospinning techniques.

Guideline development for the evaluation of visual impairment in Korea.

This guideline is developed to provide criteria for evaluating permanent impairment of the visual system as it affects an individual's ability to perform activities of daily living. This new assessment system is based on the 5th and 6th edition of American Medical Association and McBride impairment assessment system but revised on the consideration of Korean culture and simple application. This evaluation of impairment is based on an assessment of visual acuity and visual field. Especially it weighs binocular vision and binocular visual fields and the binocular vision and binocular visual fields provide 50% of weight and the right and left eye each contribute 25%. A further adjustment of the impairment rating is included at the final step of this evaluation. Functional deficits for individual adjustments include diplopia, problem of accommodation, abnormality of eyelids, tearing, cosmetic problems from cornea opacity, glare, aphakia, and dark-adaptation. The adjustment can be added to impairment rating up to 15%. Further study is necessary to revise and update of this disability evaluation that have potential problems in actual application.

Bilateral cataract surgery: a controlled clinical trial.

PURPOSE: To evaluate the efficacy and safety of simultaneous bilateral cataract surgery with respect to patient satisfaction, outcomes, and complication rates. METHODS: We conducted a prospective study of consecutive patients who had simultaneous bilateral cataract surgery on the same day or separate bilateral cataract surgery with an interval of 2 days between operations. The changes in refraction, visual acuity, degree of anisometropia, and complication rates were compared between the simultaneous bilateral cataract surgery and separate bilateral cataract surgery groups. Patient satisfaction was assessed with a questionnaire. RESULTS: Ninety-four patients who had simultaneous bilateral cataract surgery and 100 patients who had separate bilateral cataract surgery were enrolled in this study. The preoperative best-corrected visual acuity (logMAR) was 0.31 +/- 0.17 in the simultaneous bilateral cataract surgery group and 0.29 +/- 0.16 in the separate bilateral cataract surgery group, and it improved postoperatively to 0.11 +/- 0.12 in the simultaneous bilateral cataract surgery group and to 0.10 +/- 0.11 in the separate bilateral cataract surgery group. There was no significant difference between the two groups (P = 0.061). In addition, 96.8% of eyes in the simultaneous bilateral cataract surgery group and 97.0% of eyes in the separate bilateral cataract surgery group were within 1.0 diopters of the mean absolute error, and there were no sight-threatening intraoperative or postoperative complications in the two groups. CONCLUSIONS: Simultaneous bilateral cataract surgery may be an effective and safe bilateral cataract surgery option with a high degree of patient satisfaction.

Intraocular lens exchange with removal of the optic only.

PURPOSE: To evaluate the clinical outcomes of intraocular lens (IOL) exchange in patients with an opacified ACRL-C160 intraocular lens (IOL) using an optic-only removal technique. SETTING: Department of Ophthalmology, Soonchunhyang University Hospital, Seoul, Korea. METHODS: The study comprised eyes with previous phacoemulsification and implantation of a single-piece hydrophilic acrylic IOL in the capsular bag and subsequent development of severe late opacification of the IOL. In all eyes, the IOL optic was explanted; any haptic with firm adhesions was left in the capsular bag. This was followed by placement of a new IOL. The perioperative complications were evaluated, and the best corrected visual acuity (BCVA) before surgery and after surgery was compared. RESULTS: Twenty-three eyes of 20 patients were evaluated. Uneventful IOL exchange and placement of a new IOL in the bag was achieved in 9 eyes (39.1%) and in the sulcus in 13 eyes (56.5%), with posterior capsule rupture in 2 eyes (8.7%). One eye (4.3%) developed zonular dehiscence, and scleral IOL fixation was performed. The mean BCVA was 0.64 +/- 0.35 logMAR before IOL exchange and 0.24 +/- 0.20 logMAR after IOL exchange. During 41 months of follow-up, 1 eye (4.3%) each was affected by recurrent anterior uveitis and delayed zonular dehiscence. The final mean BCVA was 0.38 +/- 0.40 logMAR. There was no corneal decompensation or infectious keratitis. CONCLUSION: The optic-only removal technique was a safe and helpful procedure that allowed recovery of visual acuity because it decreased the intraoperative complication of zonular dehiscence.

Long-term stability and visual outcomes of a single-piece, foldable, acrylic intraocular lens for scleral fixation.

PURPOSE: To report long-term visual outcomes and complications of a new foldable, one-piece, acrylic posterior chamber intraocular lens with closed-loop haptics (C-flex, Rayner, UK) for scleral fixation. STUDY DESIGN: Retrospective interventional case series of 29 eyes of 29 patients who underwent scleral fixation with the C-flex intraocular lens in the absence of capsular support. METHODS: Review of 29 consecutive cases from January 2001 to December 2005 in which scleral fixation was performed with the C-flex intraocular lens. All cases were performed by a single surgeon (S.J.L.) and with an ab externo two-point scleral fixation technique. Preoperative status, intraoperative complications, and postoperative outcomes were analyzed. RESULTS: Mean best corrected visual acuity improved from 20/150 to 20/40 (P < 0.001) at 1 month and to 20/50 (P < 0.001) at mean follow-up of 41 months. Complications included clinically insignificant decentration [1 (3%)], mild intraoperative vitreous hemorrhage [1 (3%)], postoperative hyphema [2 (7%)], and transient elevated intraocular pressure [2 (7%)]. All complications were mild and resolved without the need for reoperation. CONCLUSION: Scleral fixation of the closed-loop, foldable, acrylic C-flex intraocular lens appeared to reduce operative time, was associated with minimal postoperative complications, and resulted in long-term visual improvement.

Congenital sudoriferous cyst within the orbit followed by esotropia.

PURPOSE: To report a case of congenital sudoriferous cyst of the orbit with esotropia. METHODS: A 20-day-old male, born prematurely presented with a palpable lump on left upper lid. Orbital ultrasonography including color doppler image and orbital magnetic resonance image were performed to evaluate the lid lesion. The mass was excised and histologically examined. Complete ocular examination including visual acuity, duction, version, and the presence of strabismus were performed. RESULTS: A well circumscribed round cystic mass, measuring 1.4 x 1.3 cm was noted at medial superior aspect of the left orbit. It compressed and displaced the left globe to inferior posterior position with intact optic nerve. Histopathologic examination showed the lesion to be a solitary sudoriferous cyst lined by two layers of cuboidal epithelial cells with eosinophilic cytoplasm. After the excision of the mass, limitations of extraocular muscle movements, esotropia, and amblyopia were noted. CONCLUSIONS: If an orbital cyst affects the globe or extraocular muscles, it should be excised as soon as possible to prevent strabismus and amblyopia especially in infant.

Validated LC-MS/MS method for quantification of gabapentin in human plasma: application to pharmacokinetic and bioequivalence studies in Korean volunteers.

A sensitive validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for gabapentin (GB) in human plasma has been developed and applied to pharmacokinetic (PK) and bioequivalence (BE) studies in human. In a randomized crossover design with a 1-week period, each subject received a 300 mg GB capsule. The procedure involves a simple protein precipitation with acetonitrile and separated by LC with a Gemini C(18) column using acetonitrile-10 mm ammonium acetate (20:80, v/v, pH 3.2) as mobile phase. The GB and internal standard [(S)-(+)-alpha-aminocyclohexanepropionic acid hydrate] were analyzed using an LC-API 2000 MS/MS in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 172.0 --> 154.0 and m/z 172.0 --> 126.0 for GB and IS, respectively. The assay exhibited good linearity over a working range of 20-5000 ng/mL for GB in human plasma with a lower limit of quantitation of 20 ng/mL. No endogenous compounds were found to interfere with the analysis. The accuracy and precision were shown for concentrations over the standard ranges. This method was successfully applied for the PK and BE studies by analysis of blood samples taken up to 36 h after an oral dose of 300 mg of GB in 24 healthy volunteers.