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Featured researches published by Seika Den.


Investigative Ophthalmology & Visual Science | 2011

The International Workshop on Meibomian Gland Dysfunction: Report of the Definition and Classification Subcommittee

J. Daniel Nelson; Jun Shimazaki; J.M. Benítez-del-Castillo; Jennifer P. Craig; James P. McCulley; Seika Den; Gary N. Foulks

Recommended definition of MGD: Meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. This may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease. Previous definitions and criteria of MGD: There is no firmly established definition of MGD published in the literature. Most researchers have used a criterion-based approach to describe the condition, with combinations of objective findings and measurements. Anatomic changes of the lid margin, expressibility of meibomian lipids, gland dropout by meibography, evaporimetry, and meibometry are most commonly used (Table 1). Table 1. Criteria of Meibomian Gland Dysfunction Used in Previous Works


Cornea | 2006

Association between meibomian gland changes and aging, sex, or tear function.

Seika Den; Kazuhiro Shimizu; Tsunehiko Ikeda; Kazuo Tsubota; Shigeto Shimmura; Jun Shimazaki

Purpose: To study changes in the lid margin and meibomian glands and their association with aging, sex, and tear function. Methods: We examined 354 eyes in 177 subjects (76 men and 101 women; 21-93 years; mean age, 63.0 ± 14.3 years) with no ocular symptoms or ocular surface disorders. Anatomic changes in the lid margin were studied using slit-lamp biomicroscopy. Meibomian gland function and morphology were evaluated on the basis of meibum expression and meibography, respectively. Tear function and ocular surface epithelium were assessed with the Schirmer test, by tear film break-up time, and with a fluorescein staining test. Results: Eyes with abnormal lid margin anatomy, hyposecretion of meibum, and meibomian gland dropout were seen in 26 (7.3%), 46 (12.4%), and 68 eyes (18.6%), respectively, with a significant association between each finding and aging (P = <0.0001, 0.0498, and <0.0001, respectively). In patients ≤69 years of age, no significant association was found between meibomian gland-related findings and sex. However, a high incidence of abnormal lid margin and gland dropout was noted in men ⩾70 years of age compared with women. No significant association was found between changes in the lid margin and meibomian glands and tear function in patients ⩾40 years of age. Conclusion: Among symptom-free subjects, we found that changes in the lid margin and meibomian glands were closely related to aging. Among elderly subjects, changes in the anatomic lid margin and meibomian gland morphology were observed more frequently in men than in women. Tear function showed no association with either changes in the lid margin or function of the meibomian glands.


American Journal of Ophthalmology | 2011

Prospective, randomized study of the efficacy of systemic cyclosporine in high-risk corneal transplantation.

Jun Shimazaki; Seika Den; Masahiro Omoto; Yoshiyuki Satake; Shigeto Shimmura; Kazuo Tsubota

PURPOSE Immunologic rejection remains a major cause of graft failure in high-risk corneal transplantation. This study was conducted to elucidate the efficacy and safety of systemic cyclosporine (CsA) in high-risk corneal transplantation. DESIGN Prospective, randomized, open-labeled clinical trial with a parallel-group study. METHODS Patients underwent high-risk corneal transplantation at the Department of Ophthalmology, Tokyo Dental College, Chiba, Japan. High-risk was defined as corneal neovascularization in more than 1 quadrant or a history of corneal grafting. Patients were assigned to either a systemic CsA group or a control group. Administration of CsA was continued for at least 6 months with blood CsA concentration 2 hours after administration of approximately 800 ng/mL, unless undesirable side effects developed. The main outcome measures were graft clarity, endothelial rejection, and local and systemic complications. RESULTS Forty patients were enrolled and 39 (18 men, 21 women; mean age, 67.4 ± 11.9 years) were analyzed. In the CsA group, CsA was discontinued within 6 months in 7 patients because of side effects. With a mean follow-up of 42.7 months, endothelial rejection developed in 6 and 2 eyes in the CsA and control groups, respectively. No differences were observed in the rates of graft clarity loss between the 2 groups (P = .16, Kaplan-Meier analysis). CONCLUSIONS No positive effect of systemic CsA administration for suppressing rejection in high-risk corneal transplantation was observed. With a relatively high incidence of systemic side effects, the results suggest that this protocol should not be recommended for corneal transplant recipients, especially those of advanced age.


Journal of Cataract and Refractive Surgery | 2011

Outcomes of cataract surgery in eyes with a low corneal endothelial cell density

Katsuya Yamazoe; Takefumi Yamaguchi; Kazuki Hotta; Yoshiyuki Satake; Kenji Konomi; Seika Den; Jun Shimazaki

PURPOSE: To evaluate the surgical outcomes of cataract surgery in eyes with a low preoperative corneal endothelial cell density (ECD) and analyze factors affecting the prognosis. SETTING: Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan. DESIGN: Noncomparative case series. METHODS: Eyes with a preoperative ECD of less than 1000 cells/mm2 that had cataract surgery between 2006 and 2010 were identified. Standard phacoemulsification with intraocular lenses was performed using the soft‐shell technique. The rate of endothelial cell loss, incidence of bullous keratopathy, and risk factors were retrospectively assessed. RESULTS: Sixty‐one eyes (53 patients) with a low preoperative ECD were identified. Preoperative diagnoses or factors regarded as causing endothelial cell loss included Fuchs dystrophy (20 eyes), laser iridotomy (16 eyes), keratoplasty (10 eyes), traumatic injury (3 eyes), trabeculectomy (3 eyes), corneal endotheliitis (2 eyes), and other (7 eyes). The corrected distance visual acuity improved from 0.59 ± 0.49 logMAR preoperatively to 0.32 ± 0.48 logMAR postoperatively (P<.001). The mean ECD was 693 ± 172 cells/mm2 and 611 ± 203 cells/mm2, respectively (P=.001). The mean rate of endothelial cell loss was 11.5% ± 23.4%. Greater ECD loss was associated with a shorter axial length (AL) (<23.0 mm) and diabetes mellitus. Bullous keratopathy developed in 9 eyes (14.8%) and was associated with posterior capsule rupture. CONCLUSIONS: The results suggest that modern techniques for cataract surgery provide excellent visual rehabilitation in many patients with a low preoperative ECD. Shorter AL, diabetes mellitus, and posterior capsule rupture were risk factors for greater ECD loss and bullous keratopathy. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.


Graefes Archive for Clinical and Experimental Ophthalmology | 2011

Severe donor-related Candida keratitis after Descemet's stripping automated endothelial keratoplasty.

Katsuya Yamazoe; Seika Den; Takefumi Yamaguchi; Yoichi Tanaka; Jun Shimazaki

Fungal keratitis is a rare, but severe, vision-threatening complication following keratoplasty. Fungal infection following penetrating keratoplasty has a reported incidence rate of 0.16% [1, 2]. The recent increase in Descemet’s stripping automated endothelial keratoplasty (DSAEK) has been accompanied by an increase in postoperative fungal infection, and five cases have been reported [3–6]. In three of these cases, the cause of infection was confirmed to be contaminated donor material [3, 4], a corneal venting incision was identified in the fourth case [5]. We report a much more severe case of donor-to-host transmission of fungal infection after DSAEK than those previously reported, which was treated successfully. Methods


Cornea | 2007

Achievements and future problems with component surgery of the cornea.

Tetsuya Kawakita; Motoko Kawashima; Yoshiyuki Satake; Seika Den; Machiko Tomita; Jun Shimazaki

Penetrating keratoplasty (PKP) has long been the standard procedure for treating corneal opacification. Recent advances in corneal surgery have enabled us to perform component surgery of the cornea, replacing necessary cells and tissue only instead of changing the entire layer of the cornea. Corneal components can be transplanted as lamellar sections of donor cornea or as ex vivo expanded cell sheets with or without biologic carriers. Transplantation of cultivated epithelial sheets expanded from limbal epithelium or oral mucosal epithelium, deep lamellar keratoplasty (DLKP), and deep lamellar endothelial keratoplasty (DLEK) are already in clinical application. These surgical techniques have the advantage of reducing surgical trauma, risk of immunologic rejection, and refractive error. Furthermore, severe ocular surface diseases caused by total limbal stem-cell deficiency including Stevens-Johnson syndrome can be treated by such epithelial sheet transplantation. Although limbal transplantation (LT) has also been applied for such cases, epithelial sheet transplantation has the advantage of covering the corneal surface during surgery, which may reduce postoperative inflammation. However, the success rate of clinical outcome is still not sufficient. We review the surgical technique of component surgery and compare the clinical results including visual acuity, clarity of the cornea, and neovascularization between LT and epithelial sheet transplantation and among PKP, DLKP, and DLEK in our institute. Further refinements in surgical and biologic technology may take the limits of corneal regenerative medicine to new horizons.


Cornea | 2010

How good is transplantation of corneal parts compared with penetrating keratoplasty

Seika Den; Motoko Kawashima; Machiko Shimmura; Yukari Imai; Yoshiyuki Satake; Jun Shimazaki

The concept of transplantation of corneal parts is to replace only diseased tissues, while leaving healthy host tissues intact. Advantages of the new surgical approaches include fast recovery, resistance to trauma, and less postoperative complications. Despite the theoretical benefits, however, only few data are available in terms of the pros and cons of the new surgical methods. In this review, we analyzed our data on deep anterior lamellar keratoplasty (DALK) and Descemet stripping automated endothelial keratoplasty (DSAEK). Difficulty of surgical procedure still remains in DALK, and intraoperative Descemet membrane (DM) rupture is a major concern. We recently introduced a new DM exposure technique: the double-bubble method. We also investigated the influence of DM rupture on graft survival and visual function. Other concerns in DALK are long-term stability of endothelial density and interface opacity. We also investigated safety and efficacy of subsequent cataract surgery and found that the surgery can be performed safely without significant intraoperative complications. Visual improvement was excellent, and endothelial density remained stable. Although recent increase of DSAEK is remarkable, refinements in surgical procedure are needed, especially in Asian small eyes. Recent developments in surgical technique and instruments in graft insertion are presented. DSAEK is advantageous in the management of postoperative complications, including suture-associated troubles, astigmatism, and epithelial damage. However, we encounter new complication such as graft dislocation. Surgical outcomes of our series and those of other institutes are discussed.


Eye & Contact Lens-science and Clinical Practice | 2017

Association of Epithelial Atypia With Recurrence After Surgical Excision in Conjunctival Papilloma

Hiroyuki Yazu; Murat Dogru; Jun Miyauchi; Yoichi Tanaka; Takefumi Yamaguchi; Seika Den; Yoshiyuki Satake; Kazuo Tsubota; Jun Shimazaki

Purpose: To investigate the association between recurrence of conjunctival papillomas and presence of atypical epithelial changes in patients undergoing surgical excision for conjunctival papilloma. Methods: We retrospectively reviewed 1,195 ophthalmic pathology specimens from 2004 to 2014 at Ichikawa General Hospital. Pathologic specimens of 5 patients with a final diagnosis of “conjunctival papilloma” were stained with hematoxylin–eosin, Ki 67, p53, human papillomavirus (HPV) 16 and 18 antibodies. Results: Of 1,195 patients, 5 patients (4 men, 1 woman; age range: 27∼57 years, mean age: 38.4 years) had a diagnosis of conjunctival papilloma, which constituted to 0.42% of the pathologic diagnosis made for the ophthalmology specimens. All specimens displayed multiple fronds of thickened conjunctival epithelium that enclosed cores of vascularized connective tissues. Three patients with recurrence after surgical excision demonstrated moderate to severe epithelial atypia, who also showed higher staining with Ki67 and p53 compared with patients with no recurrence. HPV16 and 18 antibodies staining did not appear to relate to recurrences. Conclusions: Conjunctival papillomas with higher positive staining for Ki67 and p53 seem to have a higher risk of recurrence even after complete surgical excision and necessitate careful follow-up.


British Journal of Ophthalmology | 2006

Disseminated keratoconjunctival epitheliopathy in a patient with systemic lupus erythematosus

Seika Den; Murat Dogru; N. Kato; Yoichi Tanaka; Shigeto Shimmura; Jun Shimazaki

Conjunctivocorneal involvement in systemic lupus erythematosus (SLE) is quite infrequent.1–3 We report the impression cytological (IC), immunohistochemical (IHC), and transmission electron microscopic (TEM) features of a case with unusual keratoconjunctival epitheliopathy refractory to medical treatment. A 76 year old woman was referred with a long history of bilateral foreign body sensation. She had been on topical antibiotics, artificial tears, corticosteroids, hyaluronate, and aciclovir without improvement. At initial examination, biomicroscopy revealed diffuse, translucent, disseminated peripheral corneal intraepithelial coin lesions with a cystic appearance (fig 1A, B), also in the bulbar conjunctiva over the limbus (fig 1C). Fluorescein staining revealed increased permeability with negative staining. Schirmer’s test was normal in both eyes. The patient had systemic and dermatological features diagnosed as SLE and had been taking prednisolone 7.5 mg/day for 1 year. Conjunctival cultures were negative for infectious processes. A thorough systemic evaluation for other systemic diseases and serum antibodies for herpes simplex virus (HSV-1, HSV-2), varicella zoster …


Investigative Ophthalmology & Visual Science | 2006

Cytokeratin 15 can be used to identify the limbal phenotype in normal and diseased ocular surfaces.

Satoru Yoshida; Shigeto Shimmura; Tetsuya Kawakita; Hideyuki Miyashita; Seika Den; Jun Shimazaki; Kazuo Tsubota

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Masahiro Omoto

Massachusetts Eye and Ear Infirmary

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