Sang In Khwarg

Seoul National University Hospital, Sŏul, Seoul, South Korea

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Publications (80)133.07 Total impact

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    ABSTRACT: Purpose: To investigate the expression of cancer stem cell (CSC) marker proteins in eyelid sebaceous gland carcinoma and evaluate the clinical significance. Methods: Archival tissue blocks from 50 cases of eyelid sebaceous gland carcinoma were tested via immunohistochemistry for 16 putative CSC markers. Levels of protein expression were analyzed alongside various clinicopathologic parameters such as metastasis-free survival time. Results: Ten patients (20%) showed nodal or distant metastasis during the follow-up period (median 35.2 months, range 1-128 months) without any mortality in our series. Among the 16 markers, ALDH1, CD44, CD133, ABCG2, Sox4, Sox9 and slug were selected for candidates of CSC markers because they were frequently and predominantly found in the tumor cells compared to control tarsus cells which showed negative or very low expression. Univariate analysis revealed that ALDH1, CD133, and ABCG2 were significantly associated with metastasis; patients with ALDH1- or CD133-positive tumors developed metastasis more frequently than patients with tumors that were negative for these markers (log-rank test, p = 0.014, p = 0.013, respectively), and diffuse expression of ABCG2 was associated with significantly shorter metastasis-free survival (log-rank test, p = 0.010). Multivariate Cox proportional hazard model revealed that ALDH1 (hazard ratio [HR] = 5.682, p = 0.038) was significantly associated with metastasis. Conclusions: Development of metastasis in eyelid sebaceous gland carcinoma might be attributed to increased number of CSCs or acquisition of dedifferentiated phenotype. Our findings suggest that CSCs are involved in the disease progression of eyelid sebaceous gland carcinoma, and in particular, expression of ALDH1 is a predictor of a poor outcome. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
    Investigative ophthalmology & visual science. 02/2015;
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    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
    The British journal of ophthalmology. 01/2015;
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    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; · 2.40 Impact Factor
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    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.
    Molecular Therapy 08/2014; · 6.43 Impact Factor
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    ABSTRACT: 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).
    Molecular vision 07/2014; 20:1037-1047. · 2.25 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    Dong Hyun Kim, Sang In Khwarg, Joo Youn Oh
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    ABSTRACT: To report a case of primary conjunctival epithelial inclusion cyst with atypical manifestation.
    Case reports in ophthalmology. 05/2014; 5(2):239-42.
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    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; · 1.80 Impact Factor
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    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. · 1.07 Impact Factor
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    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. · 1.30 Impact Factor
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    ABSTRACT: To evaluate the effectiveness of topical steroid instillation and associated factors in patients with recently developed nasolacrimal drainage stenosis.
    Journal of the Korean Ophthalmological Society 01/2014; 55(10):1418.
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    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. · 0.69 Impact Factor
  • Bo Ram Seol, Sang In Khwarg, Seong-Joon Kim
    Journal of the Korean Ophthalmological Society 01/2014; 55(3):408.
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    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 01/2014; 30(3):251-256. · 0.69 Impact Factor
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    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; · 3.02 Impact Factor
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    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; · 2.92 Impact Factor
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    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).
    Neurology 07/2013; 81(3):e17-8. · 8.30 Impact Factor
  • Cheol Kim, Min Joung Lee, Sang In Khwarg
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    ABSTRACT: To evaluate the effect of voluntary blinking and use of diluted fluorescein dye on fluorescein dye disappearance test (FDDT) in terms of diagnostic ability and test time. Prospective, nonrandomized case series. Thirty-nine patients who visited Hadong Seoul Eye Clinic between April 2009 and September 2009. All participants underwent FDDT and a lacrimal syringing test, and were divided into 2 groups according to the lacrimal syringing test results. FDDT was performed using 3 protocols: conventional FDDT (2% FDDT), FDDT with voluntary blinking (2% FDDTb), and FDDT with voluntary blinking using diluted fluorescein (0.25% FDDTb). The results were assessed by comparing initial tear meniscus height and those at 5 (2% FDDT) or 3 minutes (2% FDDTb, 0.25% FDDTb) after dye instillation. Results were considered "normal" when the tear meniscus decreased to less than 50% of its initial height, and "delayed" when it decreased to≥50%. In cases with a normal result, a half-period of dye disappearance was also recorded. Regarding diagnostic ability, the 0.25% FDDTb test had highest sensitivity and specificity among 3 protocols (100% and 80%, respectively). The half-period of dye disappearance was 3.17±1.72 minutes for 2% FDDT, 1.82±0.64 minutes for 2% FDDTb, and 1.04±0.69 minutes for 0.25% FDDTb, and showed significant difference among 3 tests (P = 0.001). The FDDT with voluntary blinking using 0.25% fluorescein had comparable diagnostic ability with the conventional FDDT, and allowed the test time to be significantly reduced.
    Canadian Journal of Ophthalmology 04/2013; 48(2):99-103. · 1.30 Impact Factor
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    ABSTRACT: BACKGROUND/AIMS: To evaluate CT and MRI findings of histopathologically proven ocular adnexa IgG4-related disease. METHODS: Study subjects included 18 patients with histopathologically proven ocular adnexal IgG4-related disease. CT (n=16) and MR (n=3) images were retrospectively evaluated for location, laterality, shape, margin, attenuation on precontrast CT images, T1 and T2 signal intensity on precontrast MRI , internal architecture, ocular adnexal lesion enhancement patterns, sialadenitis of major salivary glands, cervical lymph node enlargement and perilesional bony change. RESULTS: Lacrimal gland enlargement was observed in 16 cases. Extraglandular lesions were observed in the medial canthus (n=2) and extraconal space (n=2). Bilateral supraorbital and infraorbital nerves, pterygopalatine fossa and cavernous sinus involvement were observed in one case. All ocular adnexal lesions showed well defined margins, isoattenuation on precontrast CT images, isointensity on T1- and hypointensity on T2-weighted images, homogenous internal arcithecture and enhancement patterns and bone remodelling without destruction. CONCLUSIONS: Ocular adnexal IgG4-related disease can involve the lacrimal gland, medial canthus, extraconal space, supraorbital and infraorbital nerves, pterygopalatine fossa and cavernous sinus. A diagnosis of ocular adnexal IgG4-related disease should be considered in lesions with the typical imaging features described herein.
    The British journal of ophthalmology 02/2013; · 2.92 Impact Factor
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    ABSTRACT: Lymphomatoid papulosis (LyP) is one of the primary cutaneous CD30-positive lymphoproliferative disorders. LyP of the eyelid has rarely been reported. Herein, a case of typical LyP of the medial canthal area is reported. In addition, a literature review was performed.
    Journal of the Korean Ophthalmological Society 01/2013; 54(4):645.
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    ABSTRACT: PURPOSE: Activation 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. METHODS: Patients 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. RESULTS: Thirty-seven cases of eyelid sebaceous gland carcinoma were included in this study. Twenty-nine patients showed no metastasis, and 8 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, Chi-square 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). Conclusions: The 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 LN or distant metastasis, implying that activation of the Shh and Wnt signaling pathway is associated with aggressive behavior of the tumor.
    Investigative ophthalmology & visual science 12/2012; · 3.43 Impact Factor

Publication Stats

327 Citations
133.07 Total Impact Points


  • 2005–2014
    • Seoul National University Hospital
      • Department of Ophthalmology
      Sŏul, Seoul, South Korea
  • 1996–2014
    • Seoul National University
      • Department of Ophthalmology
      Sŏul, Seoul, South Korea
  • 2013
    • Soonchunhyang University
      Onyang, South Chungcheong, South Korea
  • 2011
    • Hallym University
      Sŏul, Seoul, South Korea
  • 2010
    • Inje University Paik Hospital
      • Department of Ophthalmology
      Goyang, Gyeonggi, South Korea
  • 2008
    • Dongguk University
      • Department of Ophthalmology
      Seoul, Seoul, South Korea
  • 2006
    • University of Ulsan
      • College of Medicine
      Urusan, Ulsan, South Korea