Namju Kim

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.

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.

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.

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.

Congenital lacrimal fistula associated with Down syndrome

BackgroundThe aim of this work is to investigate the prevalence and clinical characteristics of congenital lacrimal fistula in Down syndrome patients.MethodsThe medical records of 198 Down syndrome patients who were referred to a tertiary ophthalmology clinic from 2000 to 2010 were retrospectively reviewed to identify patients with congenital lacrimal fistula. The demographic data, clinical features, clinical management, and clinical outcomes were recorded. The main outcome measures were the presence and laterality of fistula, accompanying adnexal and oculomotor abnormalities including congenital nasolacrimal duct obstruction (NLDO), the type of surgery performed, and surgical outcome. The prevalence of congenital lacrimal fistula in Down syndrome patients was calculated upon this data.ResultsCongenital lacrimal fistula was identified in 8/198 (4.04xa0%) patients, 4 (2.02xa0%) of whom presented with bilateral lacrimal fistula. All patients that had lacrimal fistula complained of tearing from their eyes. Congenital NLDO was observed in seven of eight patients with lacrimal fistula. Five patients underwent excision of the lacrimal fistula for the improvement of cosmesis, and three of these patients also underwent lacrimal silicone intubation for NLDO. Another patient received lacrimal silicone intubation for NLDO without excision of the lacrimal fistula. Excision of the lacrimal fistula was successful in all patients; however, tearing persisted after surgery in two patients with uncorrected NLDO.ConclusionsCongenital lacrimal fistula occurs more frequently in Down syndrome patients and therefore these patients should be thoroughly examined for this abnormality. Down syndrome patients with congenital lacrimal fistula should be also examined for NLDO, because this condition is frequently observed in these patients.

Acquired lower eyelid epiblepharon in thyroid-associated ophthalmopathy of Koreans.

PURPOSEnTo investigate the prevalence and clinical features of acquired lower eyelid epiblepharon in Korean patients with thyroid-associated ophthalmopathy (TAO) and compare the pathogenic features of acquired and congenital epiblepharon.nnnDESIGNnRetrospective, nonrandomized, comparative case series, cross-sectional study.nnnPARTICIPANTSnA total of 494 Korean patients with TAO and 845 Korean patients with congenital lower eyelid epiblepharon.nnnMETHODSnThe medical records were reviewed, and the presence, location, and extent of epiblepharon were identified. Clinical features of TAO (lower eyelid retraction, exophthalmos, and elevation limitation) were compared between patients with TAO with and without epiblepharon. Acquired epiblepharon was classified into 3 types according to the location and extent. The prevalence of epiblepharon types was determined and evaluated for associations with TAO clinical features. Comparisons were made between the prevalence of epiblepharon types in acquired and congenital epiblepharon.nnnMAIN OUTCOME MEASURESnPrevalence, location, and extent of epiblepharon; association with clinical features of TAO; and difference from congenital epiblepharon.nnnRESULTSnAn acquired lower eyelid epiblepharon was found in 42 (8.5%) of 494 patients with TAO. The mean age of patients with TAO with epiblepharon (34.2±13.5 years) was significantly lower than that of patients with TAO without epiblepharon (46.5±14.1 years) (P = 0.000). Lower eyelid retraction (0.78±1.11 mm) was more severe in patients with TAO with epiblepharon than in patients without epiblepharon (0.30±0.73 mm) (P = 0.000). Lower eyelid retraction was more severe in diffuse-type acquired epiblepharon than in central-type epiblepharon (P = 0.012). Elevation limitation was more severe in central-type acquired epiblepharon than in medial-type epiblepharon (P = 0.001). The occurrence of central-type epiblepharon was higher in TAO-associated acquired epiblepharon (20 eyelids, 30.8%) than in congenital epiblepharon (27 eyelids, 1.9%, P = 0.000).nnnCONCLUSIONSnAcquired lower eyelid epiblepharon is one of the clinical features of patients with TAO. The association between lower eyelid retraction and acquired epiblepharon may lead to a better understanding of the cause of acquired epiblepharon in patients with TAO.

Risk factors for extraophthalmic involvement and treatment outcomes in patients with IgG4-related ophthalmic disease

Background/aim To analyse the clinical risk factors for extraophthalmic involvement and treatment outcomes in patients with IgG4-related ophthalmic disease (IgG4-ROD) in Korea. Methods We retrospectively reviewed medical records of 42 patients diagnosed with IgG4-ROD confirmed by a surgical biopsy during the 7-year period, between January 2009 and March 2015, at three tertiary referral centres in Korea. Data regarding patients’ demographics, clinical characteristics and radiological findings were obtained. The relapse rate was compared between systemic steroids only and combined immunosuppressant therapy. Results The mean patient age was 55.2 years (male:female ratio, 1:1). Based on the primary orbital structure affected, the IgG4-RODs were classified as dacryoadenitis (52.4%), orbital soft tissue inflammation (21.4%), trigeminal nerve involvement (11.9%) and myositis (9.5%). Extraophthalmic involvement (n=21) was associated with bilateral involvement (p=0.004), longer symptom duration (p=0.033) and a higher serum IgG4 level (p=0.034). Initial treatment regimens included attentive observation (n=7), prednisolone alone (n=22) and prednisolone plus immunosuppressive agent (n=13). During follow-up (mean, 24 months), 13 patients (37.1%) experienced relapse. In the extraophthalmic involvement group, steroid therapy alone resulted in a significantly higher relapse rate than combined immunosuppressant treatment (p=0.028). Conclusion Bilateral involvement, longer symptom duration and higher IgG4 levels were significant risk factors for extraophthalmic involvement in Korean patients with IgG4-ROD. In patients with an extraophthalmic involvement, prednisolone combined with an immunosuppressive agent was more effective for preventing recurrence than prednisolone alone.

Increased gene copy number of HER2 and concordant protein overexpression found in a subset of eyelid sebaceous gland carcinoma indicate HER2 as a potential therapeutic target.

PurposeTo identify crucial molecular alterations of receptor tyrosine kinases that can be used as potential therapeutic targets for eyelid sebaceous gland carcinoma (SbGC).MethodsThe expression levels of HER2, EGFR, C-MET, and FGFR1 were determined by immunohistochemistry (IHC). The copy numbers of the HER2, EGFR, C-MET, and FGFR1 genes were assessed by fluorescence in situ hybridization. The IHC and molecular results were correlated with the clinical parameters.ResultsA total of 49 patients with eyelid SbGC were included in this study. HER2, EGFR, C-MET, and FGFR1 protein expression was detected in 8 of 44 (16.3xa0%), 8 of 45 (17.8xa0%), 3 of 35 (8.6xa0%), and 0 of 45 patient samples, respectively. Increased copy numbers of the HER2 gene were found in 5 of 42 patient samples (11.9xa0%), including two with amplification (4.7xa0%) and three with polysomy (7.2xa0%). EGFR amplification was found in 2 of 33 (6.1xa0%) and FGFR1 amplification in 4 of 33 patient samples (12.1xa0%; high-level amplification in one and low-level amplification in three). None of the samples examined exhibited C-MET amplification. Gene copy number of the HER2 gene was correlated with its protein expression (pxa0<xa00.0001), whereas copy number of EGFR, C-MET, or FGFR1 was not correlated with protein expression. However, samples with EGFR amplification also exhibited a high level of expression of this protein.ConclusionsExtra copies of the HER2, EGFR, and FGFR1 genes were identified in a 6–12xa0% of eyelid SbGCs. A high level of concordant HER2 expression detected by immunohistochemistry can be predictive of a copy number gain of the HER2 gene. Our data suggest that the therapeutic targeting of HER2 might benefit for a subset of patients with periocular SbGCs.

Clinicopathologic Study of Chromosomal Aberrations in Ocular Adnexal Lymphomas of Korean Patients

Purpose The incidence and clinical correlation of MALT1 translocation and chromosomal numerical aberrations in Korean patients with ocular adnexal mucosa associated lymphoid tissue (MALT) lymphoma have not yet been reported. We investigated the incidence and clinicopathologic relationship of these chromosomal aberrations in ocular adnexal MALT lymphomas in a Korean population. Methods Thirty ocular adnexal MALT lymphomas were investigated for the t(11;18) API2-MALT1, t(14;18) IgH-MALT1 translocations and chromosomes 3 and 18 aneuploidies using fluorescence in situ hybridization. Patient medical records were reviewed retrospectively for information on demographics and clinical characteristics, including treatment response. Results The MALT1 gene rearrangement was found in one out of 30 cases. The t(14;18) IgH-MALT1 translocation was demonstrated in only one case (3.3%), and the t(11;18) API2-MALT1 translocation was not found in any of the cases. Trisomy 3 was observed in three ocular adnexal MALT lymphomas (10.0%), and five cases showed trisomy 18 (16.7%). Translocation positive cases also showed trisomy 18. One case of tumor relapse showed trisomy 18 only in the recurrent biopsies. There were no statistically significant correlations between chromosomal aberrations and clinical characteristics and treatment responses. Conclusions Translocations involving the MALT1 gene are not common in Korean ocular adnexal MALT lymphomas. The t(14;18) translocation was detected in only one out of 30 cases, and the t(11;18) translocation was not found at all. Furthermore, the chromosomal aberrations found in this study had no prognostic implications.

Intraoperatively Observed Lacrimal Obstructive Features and Surgical Outcomes in External Dacryocystorhinostomy

Purpose To analyze the features of lacrimal drainage system obstruction confirmed during external dacryocystorhinostomy surgeries and report the surgical outcomes. Methods We reviewed the medical records of a total of 769 cases who underwent external dacryocystorhinostomy for primary lacrimal drainage obstruction between 2005 and 2014. Data about detailed location and extent of obstruction were collected intraoperatively. The sites of obstruction were classified into nasolacrimal duct obstruction (NLDO), common canalicular obstruction (CCO), and canalicular obstruction. Lacrimal sac mucosa and lumen were grossly inspected, and the frequency of lacrimal sac changes, such as significant inflammation or fibrosis, was analyzed in cases of CCO or canalicular obstruction. The surgical success rate was also evaluated including effect of lacrimal sac status in the CCO and canalicular obstruction groups. Results Of 769 cases, primary NLDO with patent canaliculi was diagnosed intraoperatively in 432 cases (56.2%), CCO in 253 (32.9%), and canalicular obstruction in 84 (10.9%). Of 253 cases with CCO, 122 (48.2%) showed clear lacrimal sac lumen, and the other 131 (51.8%) showed significant inflammation or fibrosis of the lacrimal sac. In cases with canalicular obstruction, 35 of 84 (41.7%) showed a clear lacrimal sac, and the other 49 cases (58.3%) cases revealed mucosal changes of the lacrimal sac. The functional success rate was 87.5% for primary NLDO, 75.5% for CCO, and 72.6% for canalicular obstruction. In the CCO group, the functional success rate was lower in cases with significant lacrimal sac change (p = 0.044). Conclusions Even in patients with CCO or canalicular obstruction, a large number of cases have lacrimal sac changes, and those changes were associated with lower functional success rate.