Min Joung Lee

Mesenchymal stem/stromal cells protect the ocular surface by suppressing inflammation in an experimental dry eye.

Dry eye syndrome (DES) is one of the most common ocular diseases affecting nearly 10% of the US population. Most of the currently available treatments are palliative, and few therapeutic agents target biological pathway of DES. Although DES is a multifactorial disease, it is well-known that inflammation in the ocular surface plays an important role in the pathogenesis of DES. Mesenchymal stem/stromal cells (MSCs) have been shown to repair tissues by modulating excessive immune responses in various diseases. Therefore, we here investigated the therapeutic potential of MSCs in a murine model of an inflammation-mediated dry eye that was induced by an intraorbital injection of concanavalin A. We found that a periorbital administration of MSCs reduced the infiltration of CD4(+) T cells and the levels of inflammatory cytokines in the intraorbital gland and ocular surface. Also, MSCs significantly increased aqueous tear production and the number of conjunctival goblet cells. Subsequently, corneal epithelial integrity was well-preserved by MSCs. Together, the results demonstrate that MSCs protect the ocular surface by suppressing inflammation in DES, and suggest that MSCs may offer a therapy for a number of ocular surface diseases where inflammation plays a key role.

Dermis-Fat Graft for Treatment of Exposed Porous Polyethylene Implants in Pediatric Postenucleation Retinoblastoma Patients

PURPOSEnTo demonstrate the use of the autogenous dermis-fat graft for the treatment of porous polyethylene implant exposure and volume augmentation in postenucleation retinoblastoma children.nnnDESIGNnRetrospective, interventional case series.nnnMETHODSnTen children who received a dermis-fat graft at Seoul National University Hospital between July 1, 2005 and January 31, 2010 were included in this study. The patients had undergone unilateral enucleation for retinoblastoma, and received a subconjunctival dermis-fat graft to repair implant exposure and simultaneously correct enophthalmos. The clinical characteristics of the patients, rate of graft survival, and complications were analyzed. The cosmetic outcome was assessed using a grading system.nnnRESULTSnAll patients had enucleation using porous polyethylene implant as a primary orbital implant. The average time to exposure was 89.1 ± 22.4 months and the median size of defect was 2 × 3 mm. With a mean follow-up of 28 months, 9 of 10 patients showed well-survived graft without re-exposure. One patient who experienced a graft failure managed with implant rotation and a scleral graft. Seven patients showed significant improvement of enophthalmos.nnnCONCLUSIONSnImplantation of an autogenous dermis-fat graft is a procedure that can be effectively used to treat porous polyethylene implant exposure and simultaneously correct enophthalmos. Use of this procedure can be particularly advantageous for pediatric postenucleation patients.

Multigene methylation analysis of ocular adnexal MALT lymphoma and their relationship to Chlamydophila psittaci infection and clinical characteristics in South Korea.

PURPOSEnWe investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in ocular adnexal lymphoma (OAL) and the possible association with clinical characteristics and Chlamydophila psittaci infection.nnnMETHODSnThirty-five cases of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma cases were examined for the methylation status of nine genes using methylation-specific PCR and for the detection of C. psittaci DNA using PCR. The medical records were reviewed retrospectively. Patient demographics, clinical characteristics including the response of the lymphoma to the therapy, and C. psittaci infection status were evaluated for possible association with methylation frequencies.nnnRESULTSnCpG island methylation in nine genes was variously found as follows; DAPK (94.3%), ECAD (77.1%), MT1G (48.6%), THBS1 (37.1%), RAR-β (31.4%), p16 (20%), MGMT (5.7%), p14 (0%), and RASSF1A (0%). Methylation was not observed in any of 13 control cases. C. psittaci DNA was observed in 25 (75.8%) of 33 patients with available tumor tissues, and ECAD hypermethylation was significantly higher in C. psittaci-positive cases (P = 0.041). Promoter hypermethylation status was not correlated with clinical characteristics.nnnCONCLUSIONSnAberrant CpG island methylation of tumor suppressor genes is a frequent event in ocular adnexal MALT lymphoma. In particular, high frequencies of DAPK and ECAD methylation may be strongly correlated with ocular adnexal MALT lymphomagenesis in South Korea. Furthermore, ECAD hypermethylation is closely associated with C. psittaci infection, which may shed light on the mechanisms of bacterium-induced oncogenesis.

Lacrimal drainage obstruction in gastric cancer patients receiving S-1 chemotherapy

BACKGROUNDnThis study was conducted to determine the incidence and clinical characteristics of lacrimal drainage obstruction (LDO) in patients receiving S-1 chemotherapy.nnnPATIENTS AND METHODSnConsecutive 170 patients with gastric cancer who underwent curative surgery and received adjuvant S-1 chemotherapy were enrolled. S-1 was administered orally (40 mg/m2 b.i.d. on days 1-28 every 6 weeks) for 1 year. Ophthalmologic examinations were carried out on patients complaining of epiphora.nnnRESULTSnThirty-one patients (18%) developed epiphora. Among 31 patients, 25 underwent ophthalmologic examinations and 22 (88%) were diagnosed with LDO. The median time to the onset of LDO was 2.9 months. The most common site of obstruction was the nasolacrimal duct [86% (19/22)]; punctal [23% (5/22)] and canalicular obstruction [14% (3/22)] were also noted. In multivariate analysis, total gastrectomy [versus partial gastrectomy: hazard ratio (HR), 2.9; Pxa0=xa00.014] and creatinine clearance <50 ml/min (versus ≥50 ml/min: HR, 2.9; Pxa0=xa00.038) were independent risk factors for the development of LDO.nnnCONCLUSIONnConsidering the high incidence of LDO in patients receiving S-1 chemotherapy, oncologists should be alert to epiphora and cooperate with ophthalmologists in the early stages to improve the quality of life of patients and avoid more complicated ophthalmologic procedures.BACKGROUNDnThis study was conducted to determine the incidence and clinical characteristics of lacrimal drainage obstruction (LDO) in patients receiving S-1 chemotherapy.nnnPATIENTS AND METHODSnConsecutive 170 patients with gastric cancer who underwent curative surgery and received adjuvant S-1 chemotherapy were enrolled. S-1 was administered orally (40 mg/m2 b.i.d. on days 1-28 every 6 weeks) for 1 year. Ophthalmologic examinations were carried out on patients complaining of epiphora.nnnRESULTSnThirty-one patients (18%) developed epiphora. Among 31 patients, 25 underwent ophthalmologic examinations and 22 (88%) were diagnosed with LDO. The median time to the onset of LDO was 2.9 months. The most common site of obstruction was the nasolacrimal duct [86% (19/22)]; punctal [23% (5/22)] and canalicular obstruction [14% (3/22)] were also noted. In multivariate analysis, total gastrectomy [versus partial gastrectomy: hazard ratio (HR), 2.9; P=0.014] and creatinine clearance<50 ml/min (versus ≥50 ml/min: HR, 2.9; P=0.038) were independent risk factors for the development of LDO.nnnCONCLUSIONnConsidering the high incidence of LDO in patients receiving S-1 chemotherapy, oncologists should be alert to epiphora and cooperate with ophthalmologists in the early stages to improve the quality of life of patients and avoid more complicated ophthalmologic procedures.

Topical TSG-6 Administration Protects the Ocular Surface in Two Mouse Models of Inflammation-Related Dry Eye.

PURPOSEnTo investigate the therapeutic potential of TNF-α stimulated gene/protein (TSG)-6 in two mouse models of inflammation-mediated dry eye syndrome (DES).nnnMETHODSnWe created inflammation-mediated DES in mice by injecting concanavalin A (ConA; 10 mg/mL) into intraorbital and extraorbital lacrimal glands. Recombinant TSG-6 (1 μg in phosphate-buffered solution [PBS]) or the same volume of PBS was administered topically to eyes of the mice four times a day (QID) for 1 week. In parallel experiments, we topically applied TSG-6 (1 μg) or PBS QID to eyes of 12-week-old NOD.B10.H2b mice, a model for primary Sjögrens syndrome. Seven days later, tear production was measured, and the corneal surface was observed for epithelial defects. The number of goblet cells was evaluated in the forniceal conjunctiva. The levels of proinflammatory cytokines were analyzed in the cornea, conjunctiva, and lacrimal glands. Also, in vitro experiments were performed using cultures of corneal epithelial cells (CECs) to test the effects of TSG-6 on cell proliferation and migration.nnnRESULTSnTopical TSG-6 administration improved tear production and reduced corneal epithelial defects both in ConA-injected mice and NOD.B10.H2b mice. The conjunctival goblet cell density was higher in TSG-6-treated eyes than in PBS-treated eyes. The expression of proinflammatory cytokines in the cornea, conjunctiva, and intraorbital gland was repressed by TSG-6, while the levels of proinflammatory cytokines in the extraorbital gland were not changed. In vitro experiments revealed that TSG-6 promoted the migration of CECs, but did not affect the proliferation.nnnCONCLUSIONSnTopical TSG-6 protected the ocular surface by suppressing inflammation and promoting corneal epithelial wound healing.

Prognostic value of clinical and pathologic T stages defined by the American Joint Committee on Cancer for eyelid sebaceous carcinoma in Korea

AbstractPurposenTo investigate whether the clinical and pathologic T category classification, as defined by the American Joint Committee on Cancer (AJCC), is associated with lymph nodes (LN) or distant metastasis in patients with eyelid sebaceous carcinoma.MethodsnForty patients treated for eyelid sebaceous carcinoma at Seoul National University Hospital between March 1999 and December 2011 were retrospectively staged according to the AJCC 7th edition criteria. Three different primary tumor classifications—(1) clinical tumor size at presentation; (2) clinical AJCC T stage (cT) at presentation based not only on size, but also on the extent of involvement and (3) pathologic AJCC T stage (pT) based on histopathological examination—were compared and evaluated with regard to their association with LN or distant metastasis.ResultsIn univariate analysis, the AJCC cT (pxa0=xa00.005) and pT (pxa0=xa00.029) categories were significantly associated with metastasis, but clinical tumor size alone did not correlate with metastasis (pxa0=xa00.093). Clinical and pathologic AJCC stage T2b or higher tumors were significantly associated with metastasis compared to stage T1 or T2a tumors [odds ratio cT, 8.00 (pxa0=xa00.025); pT, 6.91 (pxa0=xa00.028)].ConclusionsThe clinical and pathologic AJCC T category has predictive value for LN or distant metastasis in eyelid sebaceous carcinoma. However, the clinically assessed largest tumor dimension alone is not an effective predictive factor. Clinicians should be aware of the increased risk of metastasis in patients with tumors of stage T2b or higher at initial presentation.

Outcome of smooth surface tunnel porous polyethylene orbital implants (Medpor SST) in children with retinoblastoma

Aim To evaluate the surgical outcome after the insertion of smooth surface tunnel porous polyethylene orbital implants (Medpor SST) in children with retinoblastoma. Methods 44 consecutive children with retinoblastoma who underwent primary enucleation and Medpor SST implantation at Seoul National University Hospital from November 2004 to August 2009, with at least 24u2005months of follow-up were included. A retrospective review of cases was performed. Results Mean age at the time of surgery was 24.7u2005months (range 1–65u2005months). The diameter of the spherical implant was 20u2005mm in 36 patients (81.8%) and 18u2005mm in 8 patients (18.2%). During a mean follow-up period of 60.1u2005months (range 26–93u2005months), there were no cases of implant exposure, extrusion or infection. Transient conjunctival thinning developed in three patients, but all resolved with conservative treatment. Anophthalmic socket complications such as lower lid malposition (retraction or entropion) (n=10, 22.7%), blepharoptosis (n=8, 18.2%) and enophthalmos (n=2, 4.5%) developed, but most showed acceptable cosmesis. Conclusions Medpor SST is relatively safe, allowing for a mean follow-up of 5u2005years in terms of implant exposure, and may be a good choice of orbital implant for children with retinoblastoma.

Associated factors of functional failure of external dacryocystorhinostomy

OBJECTIVEnTo evaluate the incidence and associated factors of functional failure of anatomically patent external dacryocystorhinostomy (DCR).nnnDESIGNnProspective, nonrandomized case series.nnnPARTICIPANTSnThirty-four consecutive patients who underwent external DCR at the oculoplasty clinic in the Department of Ophthalmology, Seoul National University Hospital between December 2008 and July 2009.nnnMETHODSnAll patients underwent external DCR for primary acquired nasolacrimal duct obstruction. The silicone tubes were removed around 6 months after the DCRs, and patients were examined 1 month after tube removal. Anatomical patency was evaluated by a nasal endoscopic dye test and lacrimal syringing test. Tearing symptoms were evaluated using Munks scoring system. Patients were divided into 2 groups according to the presence of epiphora symptom; a functional success and functional failure group, and the incidence of functional failure were calculated. Potential associated factors were also compared between 2 groups.nnnRESULTSnThis study involved 50 eyes of 34 patients, and 8 eyes of 6 patients showed significant epiphora in spite of anatomical patency (16% functional failure). We compared associated factors between 42 functionally successful and 8 functionally failed DCRs. Among variables studied, demographic factors and intraoperative surgical findings were not statistically different between the 2 groups. With respect to intranasal endoscopic findings, the shape of the rhinostomy showed significant differences between the 2 groups (p = 0.03, Fishers exact test). In the functional failure group, there were no flat shape rhinostomies. Three showed alcove shape rhinostomies, and the other 5 showed cavern shape rhinostomies.nnnCONCLUSIONSnAmong anatomically patent DCRs, the incidence of persistent epiphora was 16%. The shape of rhinostomy is a possible associated factor for functional failure after external DCR.

Expression of Shh and Wnt signaling pathway proteins in eyelid sebaceous gland carcinoma: clinicopathologic study.

PURPOSEnActivation or dysregulation of the Sonic hedgehog (Shh) and Wnt signaling pathways is suggested to lead to the development of many human malignancies. In this study, we investigated Shh and Wnt signaling protein expression in eyelid sebaceous gland carcinoma, and analyzed their correlation with clinical characteristics of the tumor.nnnMETHODSnPatients who underwent surgical resection of eyelid sebaceous gland carcinoma from 1999 to 2011 were recruited for the study. Immunohistochemical stainings of Shh signaling proteins (Shh, Gli-1, Gli-2, Gli-3, and ABCG2) and Wnt signaling proteins (Wnt, glycogen synthase kinase 3β, β-catenin, lipoprotein receptor-related protein [LRP], and c-Myc) were conducted.nnnRESULTSnThirty-seven cases of eyelid sebaceous gland carcinoma were included in this study. Twenty-nine patients showed no metastasis, and eight patients showed lymph node or distant metastasis. Shh, ABCG2, and Wnt proteins were more highly expressed in the group with metastasis than in the group without metastasis (P = 0.031, P = 0.015, and P = 0.001, respectively; χ(2) test). Patients showing high ABCG2 expression, Wnt, or LRP expression developed metastasis more commonly than those with low ABCG2, or without Wnt or LRP expression (log rank test, P = 0.019, 0.001, and 0.000, respectively).nnnCONCLUSIONSnThe group with metastasis showed higher expression levels of Shh, ABCG2, and Wnt than did the group without metastasis, and patients with strong ABCG2 expression, Wnt, or LRP expression showed higher cumulative incidence of lymph node or distant metastasis, implying that activation of the Shh and Wnt signaling pathway is associated with aggressive behavior of the tumor.

Clinicopathological Analysis of Ocular Adnexal Extranodal Marginal Zone B-Cell Lymphoma with IgG4-Positive Cells

This study aims to analyze clinical and pathological characteristics of ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL) accompanying IgG4-positive cells. Fifty patients with a diagnosis of primary non-conjunctival ocular adnexal EMZL were enrolled in this study. The number of IgG4-positive cells and the ratio of IgG/IgG4 were evaluated by immunohistochemistry in the biopsy specimens. The patients were divided into two groups based on the absolute number and the ratio of IgG4-positive cells (IgG4-posivite vs IgG4-negative groups). The demographic data, clinical staging at diagnosis, histopathological characteristics, and response to initial treatment were comparatively analyzed between the 2 groups. Five (10%) of 50 patients were defined as IgG4-positive group, and all the cases showed characteristic histological features such as extensive plasma cell infiltration and dense fibrosis. Most of these patients (4 of 5 patients) had lymphoma of the lacrimal gland. The patients from the IgG4-positive group showed a lower response rate to initial treatment (87.5 vs 33%, p = 0.03) than IgG4-negative group with a median follow-up period of 38 months. A part of the ocular adnexal EMZLs were accompanied with IgG4-positive cells. Significantly, most IgG4-positive ocular adnexal EMZLs occurred in the lacrimal gland, and can be related with a more frequent treatment failure.