Hydrogel Microneedles Extracting Exosomes for Early Detection of Colorectal Cancer.

There are several methods for early diagnosis of tumors, such as detecting circulating tumor DNAs, detecting circulating tumor cells, or imaging with tumor-targeting contrast agents. However, these assays are time-consuming and may cause patient discomfort during the biopsy collecting process. Here, we develop a facile method for early diagnosis of tumors by extracting exosomes from interstitial fluid (ISF) using hydrogel microneedles (MNs). The hydrogel MNs expand in the skin to absorb the ISF, and the tumor exosomes contained in the ISF bind with the glypican-1 antibodies inside the hydrogel of MNs. After removing the hydrogel on the MNs, exosomes are separately purified from the ISF to analyze tumor-related biomarkers. Finally, colorectal cancer can be diagnosed by ELISA for the colorectal cancer-induced model mice. This noninvasive hydrogel MN system to obtain the exosome samples would play an important role in early cancer diagnosis.

Bone Morphogenetic Protein 4 (BMP4) Enhances the Differentiation of Human Induced Pluripotent Stem Cells into Limbal Progenitor Cells.

Corneal epithelium maintains visual acuity and is regenerated by the proliferation and differentiation of limbal progenitor cells. Transplantation of human limbal progenitor cells could restore the integrity and functionality of the corneal surface in patients with limbal stem cell deficiency. However, multiple protocols are employed to differentiate human induced pluripotent stem (iPS) cells into corneal epithelium or limbal progenitor cells. The aim of this study was to optimize a protocol that uses bone morphogenetic protein 4 (BMP4) and limbal cell-specific medium. Human dermal fibroblast-derived iPS cells were differentiated into limbal progenitor cells using limbal cell-specific (PI) medium and varying doses (1, 10, and 50 ng/mL) and durations (1, 3, and 10 days) of BMP4 treatment. Differentiated human iPS cells were analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemical studies at 2 or 4 weeks after BMP4 treatment. Culturing human dermal fibroblast-derived iPS cells in limbal cell-specific medium and BMP4 gave rise to limbal progenitor and corneal epithelial-like cells. The optimal protocol of 10 ng/mL and three days of BMP4 treatment elicited significantly higher limbal progenitor marker (ABCG2, ∆Np63α) expression and less corneal epithelial cell marker (CK3, CK12) expression than the other combinations of BMP4 dose and duration. In conclusion, this study identified a successful reprogramming strategy to induce limbal progenitor cells from human iPS cells using limbal cell-specific medium and BMP4. Additionally, our experiments indicate that the optimal BMP4 dose and duration favor limbal progenitor cell differentiation over corneal epithelial cells and maintain the phenotype of limbal stem cells. These findings contribute to the development of therapies for limbal stem cell deficiency disorders.

Comparison of visual outcomes after femtosecond laser-assisted LASIK versus flap-off epipolis LASIK for myopia.

BACKGROUND: This study clinically evaluated the visual outcomes after refractive surgery for myopia using femtosecond laser-assisted in situ keratomileusis (femto-LASIK) and flap-off epipolis LASIK (epi-LASIK). METHODS: In this retrospective case series study, 40 eyes of 27 patients were divided into two groups depending on the technique used for refractive surgery. Femto-LASIK and flap-off epi-LASIK flaps were created using femtosecond laser and Epi-K™ epikeratome, respectively. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity, manifest refraction, corneal asphericity, and corneal higher-order aberrations (HOAs) were assessed pre- and postoperatively. RESULTS: The improvement in logarithm of the minimum angle of resolution (logMAR) UDVA after refractive surgery was statistically significant for both groups (P < 0.001 for all groups); it was significant better in UDVA in femto-LASIK than flap-off epi-LASIK, 0.03 ± 0.06 logMAR (femto-LASIK) and 0.54 ± 0.31 logMAR (flap-off epi-LASIK), at 1 day postoperatively; 0.02 ± 0.05 logMAR (femto-LASIK) and 0.14 ± 0.13 logMAR (flap-off epi-LASIK), at 1 week postoperatively (P < 0.001 and P = 0.019). With regard to the corneal HOAs, the increment in spherical aberration (Z4,0) was greater in flap-off epi-LASIK than femto-LASIK: 0.626 ± 0.232 µm and 0.479 ± 0.139 µm in the front cornea; 0.556 ± 0.227 µm and 0.430 ± 0.137 µm in the total cornea (P = 0.016 and P = 0.017). However, the back corneal HOA changes did not have a significant effect on the total corneal HOA changes. CONCLUSION: Femto-LASIK yielded better early visual outcomes than did flap-off epi-LASIK, but there was no significant difference between the outcomes of the two procedures, 1 week postoperatively.

Gender-differences in age-related changes of corneal astigmatism in Korean cataract patients.

BACKGROUND: This cross-sectional study investigated age-related changes in anterior, posterior, and total corneal astigmatism and evaluated sex differences in corneal astigmatism with increasing age in cataract patients. METHODS: This study evaluated eyes with cataracts from May 2009 and July 2013. All eyes underwent a complete ophthalmological examination and corneal Scheimpflug imaging by a Pentacam camera (Oculus, Wetzlar, Germany). Anterior, posterior, and total corneal astigmatism were determined. Power vector J0 and linear regression analyses were determined and compared with respect to age and sex. RESULTS: Four hundred and fifteen patients (217 men, 198 women) aged 20-89 years were evaluated. For anterior corneal astigmatism, 100% of patients who were 20-39 years old had with-the-rule (WTR) in both sexes. WTR was significantly lower in patients 80-89 years old (25.6% of men and 37.8% of women). For total corneal astigmatism, WTR also tended to decrease with increasing age: 93.3% of men and 100% of women 20-39 years old versus 20.9% of men and 31.1% of women 80-89 years old. The regression coefficient of both the anterior corneal and total corneal J0 vector values analyzed by age were - 0.018 in men and - 0.016 in women (both p < .001). CONCLUSIONS: The against-the-rule shift was faster for total corneal astigmatism than for anterior corneal astigmatism and it occurred earlier in men than in women. TRIAL REGISTRATION: Retrospectively registered. Registration number: KC15RISI0241 . Registered April 20, 2016.

Comparison of keratometric measurements between color light-emitting diode topography and Scheimpflug camera.

BACKGROUND: To determine the agreement of measurements between color light-emitting diode corneal topography (Cassini) and Scheimpflug camera keratometry (Pentacam HR). METHODS: The current retrospective study investigated 117 right eyes of 117 healthy patients before cataract surgery from June 2017 to July 2017. Steep K, flat K, mean K, astigmatism, and axis for both anterior and posterior corneal surface were measured using the two devices. The measured values were converted into J vectors such as J0 and J45. The mean difference for those measurement values were compared between the two instruments, and the agreement was evaluated using the Bland-Altman plot I. RESULTS: There were statistically significant differences in mean K (44.21D [43.34 to 45.34] and 44.30D [43.30 to 45.10] by Cassini and Pentacam [P = 0.004]) and astigmatism (0.90D [0.58 to 1.30] and 0.70D [0.40 to 1.30] by Cassini and Pentacam [P = 0.002]) on the anterior corneal surface and flat K (- 6.21D [- 6.39 to - 6.07] and - 6.30D [- 6.5 to - 6.10] by Cassini and Pentacam [P < 0.001]), mean K (- 6.39D [- 6.54 to - 6.25] and - 6.40D [- 6.60 to - 6.30] by Cassini and Pentacam [P = 0.019]), and astigmatism (0.33D [0.22 to 0.47] and 0.30D [0.15 to 0.40] by Cassini and Pentacam [P = 0.002]) on the posterior corneal surface. The mean difference (= Cassini - Pentacam) with 95% limit of agreement for mean K and astigmatism of the anterior corneal surface were 0.082D (- 0.60 to 0.76) and 0.11D (- 0.73 to 0.95) for measurements obtained by the two instruments, respectively. Regarding keratometric values from the posterior corneal surface, the mean differences for flat K, mean K, and astigmatism were - 0.081D (- 0.42 to 0.26), - 0.030D (- 0.32 to 0.26), and 0.067D (- 0.33 to 0.46), respectively. Intraclass correlation coefficients for steep K, flat K, mean K, and vector J0 were higher than 0.9 in the anterior cornea. Positive correlation in steep K, flat K, mean K, astigmatism, and J0 was found between two devices in both anterior and posterior cornea (P < 0.001). CONCLUSIONS: Corneal refractive power and astigmatism tend to be higher when measured using Cassini than Pentacam HR in both anterior and posterior cornea. The two different devices might not be used interchangeably. TRIAL REGISTRATION: Retrospectively registered. Registration number: KC17RESI0439 .

Accuracy of toric intraocular lens implantation using automated vs manual marking.

BACKGROUND: Accurate alignment of toric intraocular lens (TIOL) to steep corneal astigmatic axis is important to achieve effective postoperative results. The authors compare the accuracy of astigmatism correction using automated and manual marking in TIOL implantation during cataract surgery. METHODS: One hundred thirty-two eyes with nuclear density from Grade 2 to 4 were randomly subdivided into 2 groups (automated and manual marking). All patients underwent manual marking and the steep axis was compared to SensoMotoric Instruments (SMI). After phacoemulsification, 62 patients underwent toric IOL implantation using the SMI and 70 patients underwent toric IOL implantation using manual marking. Intraoperative measurement was the steep axis difference. Clinical measurements included preoperative and postoperative best corrected visual acuity (BCVA), and TIOL axis. RESULTS: The intraoperative steep axis difference between SMI and manual marking was 7.86 ± 6.4 degrees. The difference between the preoperative steep axis and the postoperative TIOL axis using SMI (3.63 ± 1.12 degrees) was significantly lower than that using manual marking (8.29 ± 2.23 degrees) (P < 0.05). CONCLUSIONS: The steep axis measurements may be different when using SMI vs. manual marking. The SMI is more accurate than manual marking for TIOL implantation during cataract surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12294725 , Retrospectively registered, on 20 July 2018.

Accuracy of swept-source optical coherence tomography based biometry for intraocular lens power calculation: a retrospective cross-sectional study.

BACKGROUND: To evaluate the accuracy of biometric measurements by a swept-source optical coherence tomography (SS-OCT) based biometry for intraocular lens (IOL) power calculation. METHODS: This retrospective observational study enrolled 431 patients undergoing cataract surgery. The charts were reviewed to investigate the failure rate of axial length (AL) measurement of the SS-OCT biometer, partial coherence interferometry (PCI), and A-scan ultrasonography (US) according to cataract type and severity. AL and keratometry in 164 eyes with the same IOL inserted were measured using the SS-OCT biometer, PCI, and A-scan US. The SRK/T formula was used to calculate IOL power. The mean absolute error (MAE) and percentage of eyes with a prediction error (PE) of ±0.50 D were compared. RESULTS: The AL measurement failure rate was 0.00% for A-scan US, 2.32% for the SS-OCT biometer, and 15.31% for PCI. The number of eyes measured using three devices (SS-OCT biometer, PCI, and A-scan US) was 128 (Group A) and the number of eyes measured using two devices (SS-OCT biometer and A-scan US) was 36 (Group B). The score of posterior subcapsular opacity was significantly different between two groups (p < .001). The SS-OCT biometer and PCI showed significantly lower MAE compared to A-scan US in Group A (p = 0.027). Using SS-OCT biometer, MAE showed no significant difference between Group A (0.36 ± 0.27) and Group B (0.36 ± 0.31) (p = 0.785). Whereas, MAE of A-scan US was significantly higher than Group A (0.47 ± 0.39) in Group B (0.64 ± 0.36) (p = 0.023). CONCLUSIONS: Using biometry with advanced OCT is useful in clinical practice as it is more effective in obtaining biometric measurements in the eyes with PSC and provides accurate measurements for IOL power calculation regardless of cataract type and severity. TRIAL REGISTRATION: Retrospectively registered. Registration number: KC16RISI1020 . Registered 03 January 2018.

Comparative immunological study of penetrating and anterior lamellar keratoplasty in a murine model.

In lamellar keratoplasty, the diseased part of a cornea is replaced while the healthy tissue remains lamellar keratoplasty has the advantage of better graft survival compared to penetrating keratoplasty (PK). We compared the immunological responses to PK and anterior lamellar keratoplasty (ALK) in a murine model. PK or ALK was performed using C57BL/6 donor grafts and BALB/c recipients, and graft opacity was assessed to evaluate graft rejection up to 8 weeks. We evaluated the immunological responses in both groups, which were not clinically considered as graft failure on postoperative day 21. PK mice showed reduced clinical graft survival compared to ALK mice. The mRNA expression of inflammatory mediators, such as IL-1ß, IFN-γ, and granzyme B, in grafted corneas of PK mice, was significantly increased compared to the levels in ALK mice at postoperative day 21. PK led to a higher delayed-type hypersensitivity response and IFN-γ secretion in an in vitro T cell assay from draining lymph nodes (LNs), as compared to ALK. Furthermore, PK showed increased angiogenesis and lymphangiogenesis in grafted corneas compared to ALK and led to greater infiltration of CD3+ T cells into grafted corneas and increased frequencies of mature antigen presenting cells (APC; MHC-IIhighCD11c + cells) and IL-12 + dendritic cells (DCs) in the draining LNs of transplanted mice. In conclusion, PK results in increased graft rejection compared to ALK through relatively increased neovascularization and lymphangiogenesis, which can induce infiltration of pathologic T cells and mature APC migration into grafted corneas and draining LNs.

Clinical results of the open ring PMMA guider assisted capsulorrhexis in cataract surgery.

BACKGROUND: To compare the results of continuous curvilinear capsulorrhexis(CCC) after application of an open ring-shaped guider compared with a free-hand procedure in eyes with cataracts. METHODS: This study comprised patients undergoing cataract surgery in Seoul St.Mary's Hospital, The Catholic University of Korea. Eyes were grouped depending on the capsulotomy method; CCC was performed by free-hand procedure on 94 eyes (free-hand group), and it was performed under the guidance after introduction of an open ring-shaped guider on consecutive 89 eyes (guided group). Horizontal and vertical diameter, area and circularity of capsulotomy were measured postoperatively at one day, two months and six months. Differences in parameters and the percentage of ideal capsulorrhexis were analyzed between the two groups. RESULTS: On the first postoperative day, the vertical diameter in the guided group (5.24 ± 0.16 mm) was significantly longer than that of the free-hand group (5.01 ± 0.65 mm, P = 0.019). The area of capsulotomy was larger in the guided group (21.55 ± 0.87 mm2) than that of the free-hand group (20.34 ± 2.96 mm2, P < 0.001). Circularity in the guided group (0.84 ± 0.03), was significantly greater than that of the free-hand group (0.69 ± 0.17, P = 0.036). Ideal capsulorrhexis was obtained in 60 eyes (67%) in the free-hand group and 81 eyes (86%) in the guided group. CONCLUSIONS: After introduction of an open ring-shaped guider, CCC became larger and more circular with less anterior capsular contracture. The rate of acquiring ideal capsulorrhexis was higher in the guided group than it was in the free-hand group for six months after surgery.

Effect of number and position of intraocular lens haptics on anterior capsule contraction: a randomized, prospective trial.

BACKGROUND: The present study aimed to evaluate the degree of anterior capsule contraction (capsulorhexis contraction) with three different single-piece, hydrophilic acrylic intraocular lenses (IOLs). METHODS: Patients were prospectively randomized to be implanted with one of three types of IOLs during cataract surgery: the Ophtec Precizon (IOL A), the Lucid Korea Microflex (IOL B), and the Carl Zeiss Asphina (IOL C). One week, 2 weeks, and 6 months after surgery, the area of the anterior capsule opening was measured using digital retro-illumination images after dilation of the pupil. The data were then evaluated using POCOman software. RESULTS: The study included 236 eyes of 202 patients. The area of the anterior capsule opening reduced by 3.53 ± 3.31 mm (17.06% ± 15.99%) between 1 week and 2 months post-operatively in the IOL A group, by 0.62 ± 1.32 mm (2.87% ± 6.03%) in the IOL B group, and by 1.09 ± 1.53 mm (4.72% ± 6.10%) in the IOL C group. The IOL B group showed minimal anterior capsule contraction 2 months after surgery (p < 0.001). CONCLUSIONS: IOLs with a four-plate haptic design (IOL B) showed more anterior capsular stability than those with a two-loop plate haptic (IOL A) or two-plate haptic (IOL C) design. The number and position of haptics in a capsular bag may affect anterior capsule contraction. We assume that supporting the zonules evenly may play a role in anterior capsular stability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76566080 , Retrospectively registered (Date of registration: 14 Feb 2018).

Influence of across-pupil sutures on the optical quality of intraocular lenses.

PURPOSE: In cases of pupillary capture after previous transscleral fixation of an intraocular lens (IOL), an across-pupil suture technique is sometimes used to stabilize the IOL. We investigated the optical effects of 10-0 polypropylene sutures placed across the pupil. METHODS: Optical performance was evaluated using the optical bench metrology system, and a single-piece IOL was used in an optical bench system consisting of a model eye, a high-resolution Hartmann-Shack wave front sensor, and an image capturing device with 2.0, 3.0, 4.0, and 4.5 mm apertures with distance focus. To simulate across-pupil sutures, two 10-0 polypropylene sutures were placed 2 mm apart across the pupil. The focus image, spherical aberration, and image quality were measured and compared with and without sutures. RESULTS: When pupil size increased, spherical aberration increased, irrespective of sutures. No difference was found in spherical aberration with and without sutures, and image qualities at 17.6 and 35.2 cycles per degree were not affected by the across-pupil sutures. CONCLUSIONS: The differences in optical quality using across-pupil 10-0 polypropylene sutures were clinically negligible.

A Novel Peptide Derived From Tissue-Type Plasminogen Activator Potently Inhibits Angiogenesis and Corneal Neovascularization.

The recombinant protein TK1-2, which consists of two kringle domains of tissue-type plasminogen activator (t-PA), inhibits angiogenesis and tumor growth. ɪn this study, we examined the anti-angiogenic activities of peptides derived from kringle 2 domain of t-PA to identify the functional core sequence. Seven peptides were constructed from the kringle 2 sequence, based on the structure and characteristics of amino acid residues, and were analyzed for their inhibitory effects on endothelial cells (ECs). Among them, TP-7 (derived from a ß-sheet motif) potently inhibited proliferation, tube formation, and migration of ECs in a dose-dependent manner, whereas truncation of 3-9 amino acid residues from either N or C terminus of TP-7 abrogated its inhibitory effects on ECs. TP-7 also potently inhibited angiogenesis in a Matrigel plug assay in vivo. Moreover, TP-7 dose-dependently suppressed corneal neovascularization induced by an acute chemical burn in a rat model. At the molecular level, TP-7 inhibited VEGF- or bFGF-induced phosphorylation of FAK and ERK1/2 and drastically disrupted VEGF- or bFGF-induced formation of stress fibers and focal adhesion complexes. In addition, TP-7 markedly suppressed attachment and spreading of ECs on a collagen type I or fibronectin matrix. Adhesion of ECs to immobilized TP-7 increased dose-dependently, which was disrupted strongly by pretreatment with soluble TP-7 and slightly by an integrin α2ß1-blocking antibody. These results suggest that TP-7 is a potent anti-angiogenic peptide in part affecting the integrin α2ß1-dependent pathway and that it can be used for treatment of corneal neovascularization by targeting VEGF and non-VEGF pathways. J. Cell. Biochem. 118: 1132-1143, 2017. © 2016 Wiley Periodicals, Inc.

Genome-wide association study using the ethnicity-specific Japonica array: identification of new susceptibility loci for cold medicine-related Stevens-Johnson syndrome with severe ocular complications.

A genome-wide association study (GWAS) for cold medicine-related Stevens-Johnson syndrome (CM-SJS) with severe ocular complications (SOC) was performed in a Japanese population. A recently developed ethnicity-specific array with genome-wide imputation that was based on the whole-genome sequences of 1070 unrelated Japanese individuals was used. Validation analysis with additional samples from Japanese individuals and replication analysis using samples from Korean individuals identified two new susceptibility loci on chromosomes 15 and 16. This study might suggest the usefulness of GWAS using the ethnicity-specific array and genome-wide imputation based on large-scale whole-genome sequences. Our findings contribute to the understanding of genetic predisposition to CM-SJS with SOC.

Bortezomib inhibits proliferation, migration, and TGF-ß1-induced epithelial-mesenchymal transition of RPE cells.

Purpose: Nuclear factor kappa B (NF-κB) plays an important role in the epithelial-mesenchymal transition (EMT) of RPE cells. We investigated the effects of a proteasome inhibitor, bortezomib, on the EMT in RPE cells. In addition, we assessed the influence of bortezomib on regulation of the NF-κB pathway during this process. Methods: After treatment with various concentrations of bortezomib, cell viability was analyzed with the water-soluble tetrazolium salt-8 assay, cell-cycle regulation was evaluated with flow cytometry, and cell migration was monitored with in vitro wound healing and Transwell migration assays. To induce fibroblastoid transformation, the RPE cells were treated with recombinant human transforming growth factor (TGF)-ß1 (10 ng/ml), and western blot and immunocytochemical analyses were performed to evaluate altered expression of EMT markers after treatment with bortezomib. To verify the effect of bortezomib on shrinkage by myofibroblastic transformation, a contraction assay of the RPE-collagen gel lattice was performed. Results: Treatment with bortezomib decreased RPE viability in a dose-dependent manner, and flow cytometry revealed that these effects were due to arrest of the G2/M phase cell-cycle. In the in vitro wound healing and Transwell migration assays, treatment with 20 nM bortezomib significantly impeded RPE migration. Treatment with bortezomib also significantly inhibited TGF-ß1-induced transdifferentiation of the RPE cells. The effects on proliferation, migration, and the EMT were mediated by regulation of the NF-κB signaling pathway. In addition, bortezomib inhibited contraction of the RPE-collagen gel lattices. Conclusions: Bortezomib inhibits myofibroblastic transformation of RPE cells by downregulating NF-κB expression and prevents contraction of the RPE-collagen gel matrix. Thus, bortezomib represents a candidate putative therapeutic agent for management of retinal fibrotic diseases.

Changes of meibomian glands in the early stage of post hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is the most effective cure for hematologic malignancies. Graft-versus-host disease (GVHD) is a major complication following allogeneic HSCT, which significantly affects non-relapse mortality. And ocular manifestations of GVHD are known to occurin 60-90% of patients with chronic GVHD. Although the pathogenesis of ocular GVHD is not clearly known, it is known to progress into inflammation and fibrosis through presentation of antigens on CD4 and CD8 T cells. There is much evidence that the ocular surface and meibomian glands are severely damaged in ocular GVHD patients, and there are few observational studies on the early changes. In this review, we will discuss the various changes in the meibomian glands and ocular surface, and tear dynamics in the early stage following HSCT. These results show that tear film break-up time (TFBUT) decreased and the corneal staining score was significantly higher 2-3 months after HSCT. The upper eyelid and total eyelid meiboscore increased after 3 months following HSCT. The information of the early changes of meibomian glands morphology would be helpful to further examine the pathogenesis of meibomian gland dysfunction.

Morphological evaluation for diagnosis of dry eye related to meibomian gland dysfunction.

The evaluation of morphological changes of the acini in the meibomian glands is important for the diagnosis and management of dry eye related to meibomian gland dysfunction. While several tools have been developed to detect meibomian gland structure, infrared imaging is generally used in clinical settings. Unlike the lipid component analysis of tear film in which quantitative analysis is possible, the meibomian glands are limited to qualitative analysis because of the low image quality of the diagnostic tools. This review describes diagnostic tools, especially in terms of morphological evaluation of the acini, which are visualized by the existence of lipid within them.

Reverse pupillary block after implantation of a scleral-sutured posterior chamber intraocular lens: a retrospective, open study.

BACKGROUND: To report the clinical features of patients with reverse pupillary block (RPB) after scleral-sutured posterior chamber intraocular lens (PC IOL) implantation and biometric changes after laser peripheral iridotomy (LPI). METHODS: Eight patients attending our hospital's ophthalmology outpatient clinic, who developed RPB after implantation of a scleral-sutured PC IOL due to subluxation of the crystalline lens or IOL, were investigated in this retrospective, observational study. RESULTS: Preoperative evaluations showed angle pigmentation in all cases and iridodonesis in 2 cases. Two subjects had used an α1A-adrenoceptor antagonist for benign prostatic hyperplasia. Pars plana or anterior partial vitrectomy was performed in all cases. All eyes showed an extremely deep anterior chamber, a concave iris configuration, and contact between the IOL optic and the iris at the pupillary margin. Pupil capture was detected in 2 cases. The mean (± SD) anterior chamber angle (ACA) was 89.91 ± 10.06°, and the anterior chamber depth (ACD) was 4.42 ± 0.16 mm before LPI. After LPI, the iris immediately became flat with a decreased ACA (51.70 ± 2.59°; P = 0.018) and ACD (4.14 ± 0.15 mm; P = 0.012). After LPI, the intraocular pressure decreased from 19.75 ± 3.77 mmHg to 15.63 ± 4.30 mmHg (P = 0.011), and the spherical equivalent decreased from -0.643 ± 0.385 D to - 0.875 ± 0.505 D (P = 0.016). CONCLUSION: Concomitant vitrectomy, angle pigmentation, and iridodonesis may be risk factors for RPB after scleral-sutured PC IOL implantation. LPI is effective for relieving the RPB.

Clinical Features of Infectious Keratitis Caused by Propionibacterium Acnes.

PURPOSE: Propionibacterium acnes is a commensal bacteria whose pathogenicity in infectious keratitis is unclear. In this study, we report infectious keratitis cultured with P. acnes and evaluate its clinical characteristics. METHODS: All cases of infectious keratitis submitted to the microbiology laboratory of St. Mary's Hospital of Seoul between January 2013 and April 2014 were reviewed. Nonpretreated cases that were positive for P. acnes were identified, and clinical characteristics and treatment outcomes were studied. RESULTS: Of 132 cultures submitted to the microbiology laboratory, 89 (67.4%) were positive for growth, and a total of 16 (17.9%) of the 89 cases yielded P. acnes in culture medium. Infectious keratitis that was positive for P. acnes was generally small (62.5%) with deep stromal infiltration (81.25%) and a peripheral location (56.25%). The average incubation period was 11.06±5.76 days, and the average time to reepithelialization was 23.50+13.52 days. All the cases of P. acnes evaluated in this report responded well to medical treatment. CONCLUSIONS: Infectious keratitis with P. acnes is not uncommon and can be confused with other Gram-positive cocci. Thus, P. acnes should be suspected in small-sized keratitis with an unusually long incubation period.

Diquafosol promotes corneal epithelial healing via intracellular calcium-mediated ERK activation.

Diquafosol is known as a purinergic P2Y2 receptor (P2Y2R) agonist that stimulates water and mucin secretion from conjunctival epithelial cells and goblet cells, leading to tear film stability in dry eye. However, its effect on corneal epithelial healing has not yet been elucidated. The aim of the present study was to evaluate the effect of diquafosol on corneal epithelial healing in vivo and on P2Y2R-related downstream signaling pathways in vitro. We administered 3% diquafosol ophthalmic solution on 3 mm-diameter epithelial defects made in rat corneas and assessed the wound closure over time. Corneal epithelial healing was significantly accelerated in diquafosol-treated eyes compared to control eyes at 12 and 24 h. During wound healing, P2Y2R staining appeared stronger in the re-epithelized margin near the wound defect. To evaluate whether diquafosol stimulates epidermal growth factor receptor/extracellular-signal-regulated kinase (EGFR/ERK)-related cell proliferation and migration, simian virus 40-transfected human corneal epithelial (THCE) cells were used for in vitro experiments. Cell proliferation was accelerated by diquafosol at concentrations from 20 to 200 µM during 48 h, but inhibited at concentrations over 2000 µM. The intracellular calcium ([Ca(2+)]i) elevation was measured in diquafosol (100 µM)-stimulated cells using Fluo-4/AM ([Ca(2+)]i indicator). [Ca(2+)]i elevation was observed in diquafosol-stimulated cells regardless of the presence of calcium in media, and suramin pretreatment inhibited the calcium response. The effect of diquafosol on phosphorylation of EGFR, ERK and Akt, and cell migration was determined by western blotting and in vitro cell migration assay. Diquafosol induced phosphorylation of EGFR at 2 min post-stimulation, and phosphorylation of ERK at 5 min post-stimulation. Phosphorylation of ERK was attenuated in cells pretreated with suramin or BAPTA/AM ([Ca(2+)]i chelator), and partially with AG1478 (EGFR inhibitor). Likewise, diquafosol-treated cells showed acceleration of gap closure in cell migration assay, which was inhibited by suramin, BAPTA/AM, AG1478, and U0126 (MEK inhibitor). These studies demonstrate that diquafosol is effective in promoting corneal epithelial wound healing and that this effect may result from ERK-stimulated cell proliferation and migration via P2Y2R-mediated [Ca(2+)]i elevation.

The Influence of Overnight Orthokeratology on Ocular Surface and Meibomian Glands in Children and Adolescents.

PURPOSE: The aim of this study was to investigate the influence of overnight orthokeratology (OOK) on ocular surface and meibomian glands in children and adolescents. METHODS: Prospective, noncomparative study included the ocular surface disease index (OSDI), tear osmolarity, corneal and conjunctival fluorescein staining, tear film breakup time (TBUT), the Schirmer I test, and meiboscore using noncontact meibography. Immunofluorescence confocal microscopy of interleukin-1ß (IL1ß), interleukin-6 (IL6), epidermal growth factor (EGF), and matrix metalloproteinase (MMP)-9 using impression cytology filter paper was performed. The tests were performed before and at 6, 12, 24, and 36 months after OOK wear. RESULTS: Fifty-eight subjects using OOK were observed. Significant increases in OSDI score (P=0.0009) and corneal and conjunctival staining score (P<0.0001) were observed compared with baseline values at 36 and 24 months, respectively. Ocular surface and meibomian changes were noted in 2 patients (3.5%). One patient exhibited an increase in OSDI score, concurrent with a decrease in TBUT at 36 months and minor loss of the meibomian gland at the distal portion of the lower lid at 24 months. The other patients exhibited the development of papillary hypertrophy and meibomian gland distortion at 24 months. No significant changes were detected in IL1ß, IL6, EGF, or MMP expression after OOK use. CONCLUSION: Based on the findings, OOK was a relatively safe modality. However, given the potential changes in the meibomian gland and tear film stability, special attention must be paid to children with baseline meibomian gland distortions or a history of allergic conditions.