[Show abstract][Hide abstract] ABSTRACT: Ocular adnexal IgG4-related sclerosing disease (IgG4-SD) has been categorized as a novel disease entity. It is characterized by stromal sclerosis and an infiltration of mass-forming lymphoplasmic cells containing many IgG4-positive plasma cells. Although ocular adnexal tissue involvement has been increasingly reported, a focal nodular sub-brow mass is not typical in an IgG4-SD presentation. We report a rare case of probable ocular adnexal IgG4-SD that clinically mimicked eyelid pilomatrixoma.
A 42-year-old woman presented with a nodular mass in her left sub-brow area. The initial clinical impression of her lesion was eyelid pilomatrixoma. However, the final pathologic diagnosis was IgG4-SD, but extranodal marginal zone B-cell lymphoma could not be excluded. The patient underwent testing to determine tumor malignancy and systemic IgG4-SD involvement. Laboratory testing showed normal IgG and IgG4 serum levels and imaging revealed no remarkable findings. Oral prednisolone was administered and slowly tapered to manage the possible remnant lesion and to prevent disease recurrence. Two years after initiating therapy, there was no evidence of relapse. The patient is under close surveillance for signs of recurrence, systemic involvement, and potential malignant transformation.
We found an unusual case of probable ocular adnexal IgG4-SD, which presented as a unilateral restricted mass involving the sub-brow area. Although the mass was surgically removed, systemic steroid treatment and long-term surveillance were initiated due to the possibility of recurrence, the potential association with systemic disease, and the potential development of extranodal mucosa-associated lymphoid tissue (MALT) lymphoma.
[Show abstract][Hide abstract] ABSTRACT: To investigate the therapeutic potential of TNF-α stimulated gene/protein (TSG)-6 in two mouse models of inflammation-mediated dry eye syndrome (DES).
We 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 Sjögren's 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.
Topical 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.
Topical TSG-6 protected the ocular surface by suppressing inflammation and promoting corneal epithelial wound healing.
[Show abstract][Hide abstract] ABSTRACT: To identify crucial molecular alterations of receptor tyrosine kinases that can be used as potential therapeutic targets for eyelid sebaceous gland carcinoma (SbGC).
The 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.
A 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 (16.3 %), 8 of 45 (17.8 %), 3 of 35 (8.6 %), and 0 of 45 patient samples, respectively. Increased copy numbers of the HER2 gene were found in 5 of 42 patient samples (11.9 %), including two with amplification (4.7 %) and three with polysomy (7.2 %). EGFR amplification was found in 2 of 33 (6.1 %) and FGFR1 amplification in 4 of 33 patient samples (12.1 %; 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 (p < 0.0001), 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.
Extra copies of the HER2, EGFR, and FGFR1 genes were identified in a 6-12 % 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.
Journal of Cancer Research and Clinical Oncology 07/2015; DOI:10.1007/s00432-015-2009-z · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
PLoS ONE 06/2015; 10(6):e0131458. DOI:10.1371/journal.pone.0131458 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a paucity of data in the literature on the surgical management of conjunctival dermolipoma. In this study, we report outcomes of a partial mass excision technique (excision of the portion visible when eyes open) and free conjunctival autograft.
Medical records of 13 patients with dermolipoma who had undergone partial mass excision at Seoul National University Hospital from January 1999 to May 2014 were retrospectively reviewed. After resection of the visible part of tumour, including the overlying thick surface conjunctiva, the conjunctival defects were reconstructed with free conjunctival autograft harvested from the contralateral superior bulbar area.
The median postoperative follow-up period was 5 months (range 1-84 months). The cosmetic surgical results were satisfactory in all 13 patients. Three patients showed thick texture on the grafted surgical area postoperatively, but there was no significant scar formation resulting in restrictive symblepharon or eye movement limitation. There were no other significant complications, such as blepharoptosis, diplopia or keratoconjunctivitissicca during the follow-up period.
Partial mass (visible part only) excision, including that of the overlying thick conjunctiva, and free conjunctival autograft from the opposite eye, is a relatively simple and effective technique for the surgical management of conjunctival dermolipoma.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
British Journal of Ophthalmology 01/2015; 99(8). DOI:10.1136/bjophthalmol-2014-306328 · 2.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ocular adnexal lymphoma (OAL) has been associated with Chlamydophila psittaci infection, for which doxycycline has been suggested as a treatment option. We conducted this study to evaluate the long-term results of first-line doxycycline treatment in patients with OAL. Ninety patients with histologically confirmed OAL with marginal zone B cell lymphoma were enrolled. Each patient received one or two cycles of doxycycline (100 mg bid) for 3 weeks. After a median follow-up period of 40.5 months (8-85), the 5-year progression-free survival (PFS) rate was 60.9 %. All patients were alive at the last follow-up date. Thirty-one patients (34 %) showed local treatment failure without systemic spread. However, PFS rate in these patients was 100 % after salvage chemotherapy and/or radiotherapy. PFS was independently predicted in multivariate analysis by the tumor-node-metastasis (TNM) staging (hazard ratio [HR], 4.35; 95 % confidence interval [CI], 2.03-9.32; P < 0.001) and number of cycles of doxycycline (HR, 0.31; 95 % CI, 0.14-0.69; P = 0.004). No serious adverse event was reported during doxycycline therapy. In conclusion, first-line doxycycline therapy was effective and safe. Patients who failed to respond to doxycycline therapy were successfully salvaged with chemotherapy and/or radiotherapy without compromising long-term outcomes. Patients with T1N0M0 disease could be considered good candidates for first-line doxycycline.
Annals of Hematology 10/2014; 94(4). DOI:10.1007/s00277-014-2240-8 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dry eye syndrome (DES) is one of the most common ocular diseases affecting nearly 10% of the U.S. 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.Molecular Therapy (2014); doi:10.1038/mt.2014.159.
[Show abstract][Hide abstract] ABSTRACT: Purpose
To compare genome-wide DNA methylation profiles according to Chlamydophila psittaci (Cp) infection status and the response to doxycycline treatment in Korean patients with ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL).
Twelve ocular adnexal EMZL cases were classified into two groups (six Cp-positive cases and six Cp-negative cases). Among the 12 cases, eight were treated with doxycycline as first-line therapy, and they were divided into two groups according to their response to the treatment (four doxy-responders and four doxy-nonresponders). The differences in the DNA methylation states of 27,578 methylation sites in 14,000 genes were evaluated using Illumina bead assay technology. We also validated the top-ranking differentially methylated genes (DMGs) with bisulfite direct sequencing or pyrosequencing.
The Infinium methylation chip assay revealed 180 DMGs in the Cp-positive group (74 hypermethylated genes and 106 hypomethylated genes) compared to the Cp-negative group. Among the 180 DMGs, DUSP22, which had two significantly hypomethylated loci, was validated, and the correlation was significant for one CpG site (Spearman coefficient=0.6478, p=0.0262). Regarding the response to doxycycline treatment, a total of 778 DMGs were revealed (389 hypermethylated genes and 336 hypomethylated genes in the doxy-responder group). In a subsequent replication study for representative hypomethylated (IRAK1) and hypermethylated (CXCL6) genes, the correlation between the bead chip analysis and pyrosequencing was significant (Spearman coefficient=0.8961 and 0.7619, respectively, p<0.05).
Ocular adnexal EMZL showed distinct methylation patterns according to Cp infection and the response to doxycycline treatment in this genome-wide methylation study. Among the candidate genes, DUSP22 has a methylation status that was likely attributable to Cp infection. Our data also suggest that the methylation statuses of IRAK1 and CXCL6 may reflect the response to doxycycline treatment.
[Show abstract][Hide abstract] ABSTRACT: To investigate the clinical and histopathological features of inflammatory lesions of the lateral canthal subconjunctival area.
This is a retrospective case series of 12 patients with inflammatory subconjunctival masses in the lateral canthal area. All patients included in this study were treated at Seoul National University Hospital or Seoul National University Bundang Hospital between 2006 and 2012. Clinical data were obtained from the medical records. Histopathologic findings were thoroughly reviewed.
There was a woman predominance in the study group (10:2), and the median age at presentation was 39 years (range 33-70). Common symptoms included conjunctival injection, sticky discharge, and pain or discomfort. Histopathologically, all lesions originated from ductules of the lacrimal gland. Two cases showed cysts containing clear fluid with mild inflammation. One case showed lacrimal ductulitis without cyst formation. Nine cases showed lacrimal ductal cysts with varying periductal inflammation, and the contents were pinkish, amorphous materials in 7 cases. Embedded cilia were found in 8 cases.
Inflammatory lesions of the lateral canthal subconjunctival area all originated from lacrimal gland ductules, showing a variable histopathologic spectrum of inflammation and cyst formation. Cilia impaction was a very frequently observed finding.
Ophthalmic plastic and reconstructive surgery 05/2014; 30(3):251-256. DOI:10.1097/IOP.0000000000000087 · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
To report a case of primary conjunctival epithelial inclusion cyst with atypical manifestation.
A 66-year-old woman presented with a yellowish, subconjunctival mass extending from the corneal limbus to the medial canthus in the left eye. Clinical, radiological and histological assays were performed.
The mass was well-delineated, and the overlying conjunctiva was normal. An enhanced axial orbit computed tomography scan showed a 7.7 × 3.6 mm, well-demarcated, convex-shaped enhanced mass. Neither a connection to the orbital area nor extrusion of intraconal fat was observed. Histological examination revealed that the lesion was a cystic mass that was lined by nonkeratinized, stratified squamous epithelium, and filled with mucous materials and cellular debris. The histologic diagnosis was consistent with conjunctival epithelial inclusion cyst.
A careful examination using clinical, radiologic and histological studies is essential for the differential diagnosis of subconjunctival mass.
Case Reports in Ophthalmology 05/2014; 5(2):239-42. DOI:10.1159/000365914
[Show abstract][Hide abstract] ABSTRACT: To 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.
Forty 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.
In univariate analysis, the AJCC cT (p = 0.005) and pT (p = 0.029) categories were significantly associated with metastasis, but clinical tumor size alone did not correlate with metastasis (p = 0.093). 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 (p = 0.025); pT, 6.91 (p = 0.028)].
The 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.
Japanese Journal of Ophthalmology 04/2014; 58(4). DOI:10.1007/s10384-014-0321-9 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the clinical characteristics and treatment outcomes of patients with congenital membranous punctal obstruction.
The medical records of patients who underwent surgical treatment for congenital membranous punctal obstruction between 1999 and 2011 were retrospectively reviewed. The demographic data and clinical presentations of the patients were analyzed. Surgical intervention methods and treatment results were also evaluated.
A total of 51 puncta in 31 eyes of 23 patients with congenital membranous punctal obstruction were included. Of the 31 eyes, 20 had both upper and lower punctal obstruction and 11 had single punctal obstruction. Up to 2008, 10 patients underwent simultaneous punctoplasty and silicone tube intubation; 7 were under 10 years of age and required general anesthesia for the procedure. All showed patent puncta without epiphora postoperatively. Of the 13 patients treated after 2008, 11 children underwent punctoplasty and lacrimal irrigation under general anesthesia. Nasolacrimal duct obstruction (NLDO) was found in 6 of the 11 patients, and combined silicone tube intubation was performed; 2 adults with both upper and lower punctal obstruction underwent only punctoplasty under local anesthesia. All puncta were opened sufficiently, but epiphora remained in 1 patient due to NLDO, requiring subsequent silicone intubation. Overall, NLDO was found in 7 of 13 patients.
Congenital membranous punctal obstruction can be successfully treated by punctoplasty alone. Because this is often associated with NLDO, the nasolacrimal system should also be thoroughly evaluated.
Journal of AAPOS: the official publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus 04/2014; 18(2):159-61. DOI:10.1016/j.jaapos.2013.12.006 · 1.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the incidence and associated factors of functional failure of anatomically patent external dacryocystorhinostomy (DCR).
Prospective, nonrandomized case series.
Thirty-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.
All 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 Munk's 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.
This 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, Fisher's 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.
Among 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.
Canadian Journal of Ophthalmology 02/2014; 49(1):40-4. DOI:10.1016/j.jcjo.2013.08.006 · 1.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a paucity of data in the literature on the surgical management of lower eyelid marginal entropion. In this study, the authors report outcomes of a surgical technique of eyelid margin splitting and anterior lamellar reposition in patients with lower eyelid marginal entropion.
The medical records for 30 eyelids from 22 patients with lower eyelid marginal entropion who had undergone eyelid margin splitting and anterior lamellar repositioning at Seoul National University Hospital from January 2004 to December 2012 were retrospectively reviewed. Success was defined as the lack of any lash in contact with the globe, no need for a second procedure, the complete resolution of symptoms, and acceptable cosmesis at the final follow up.
The mean follow-up duration was 16.7 months. The split eyelid margin exhibited good wound healing in each case, but trichiasis recurred postoperatively in 3 of 30 eyelids, even though the eyelid margin was ultimately well positioned. That is, the overall success rate was 90%. Of the 3 eyelids with recurrent trichiasis, 2 required additional electrolysis to remove irritated cilia, but the other did not require to be treated. In the latter case, the trichiasis observed was fine, focal, and unaccompanied by symptoms or corneal lesions. There was no significant complication such as secondary ectropion or eyelid retraction.
Eyelid margin splitting and anterior lamellar repositioning achieve success with a low rate of complications among patients with lower eyelid marginal entropion.
Ophthalmic plastic and reconstructive surgery 01/2014; 30(1):51-6. DOI:10.1097/IOP.0000000000000008 · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prognosis of eyelid sebaceous gland carcinoma is largely unpredictable and there are few practically available markers for predicting patients' prognosis. Dysregulation of cell cycle progression is strongly associated with the development of cancer and the cancer prognosis. We investigated the expression of cell cycle regulatory proteins in eyelid sebaceous gland carcinoma and estimate their value as prognostic predictors. Forty-three cases of eyelid sebaceous gland carcinoma were included in this study. Immunohistochemistry for the p53, p21, p27, cyclin E, p16, cyclin D1, and phosphorylated Rb (pRb) proteins was performed using archival paraffin blocks. Correlations between clinical features and protein expression were evaluated statistically. Nine patients showed lymph node or distant metastasis, and the remaining patients showed localized disease. High expression of p21, p27, cyclin E, and p16 was found in the majority of tumor cell nuclei, whereas these proteins were rarely expressed in the normal sebaceous glands. However, pRb was focally lost in a subset of cases. Patients showing diffuse p27 expression developed metastasis less commonly than those with negative or focal p27 expression (log-rank test, p = 0.008). Aberrant expression of cell cycle regulatory proteins was observed in eyelid sebaceous gland carcinoma, suggesting that cell cycle dysregulation is involved in the pathogenesis of this tumor. Decreased p27 expression is a predictive biomarker of an unfavorable prognosis of eyelid sebaceous gland carcinoma.
Experimental Eye Research 11/2013; DOI:10.1016/j.exer.2013.10.022 · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the surgical outcome after the insertion of smooth surface tunnel porous polyethylene orbital implants (Medpor SST) in children with retinoblastoma.
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 24 months of follow-up were included. A retrospective review of cases was performed.
Mean age at the time of surgery was 24.7 months (range 1-65 months). The diameter of the spherical implant was 20 mm in 36 patients (81.8%) and 18 mm in 8 patients (18.2%). During a mean follow-up period of 60.1 months (range 26-93 months), 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.
Medpor SST is relatively safe, allowing for a mean follow-up of 5 years in terms of implant exposure, and may be a good choice of orbital implant for children with retinoblastoma.
The British journal of ophthalmology 09/2013; 97(12). DOI:10.1136/bjophthalmol-2013-303481 · 2.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 40-year-old woman presented with horizontal diplopia and right proptosis for 1 month. She had esotropia and right abducens nerve palsy. Pupils were small and equal and there was no relative afferent pupillary defect. A cutaneous capillary malformation, hypertrophy of bone and soft tissue, and varicose veins on lower extremities were consistent with the diagnostic triad of Klippel-Trenaunay syndrome (KTS) (figure 1).(1) Orbital CT revealed multiple giant intracranial aneurysms (figure 2).