Publications by authors named "Kazuko Kitagawa"

18 Publications

  • Page 1 of 1

Clinical features and symptoms of IgG4-related ophthalmic disease: a multicenter study.

Jpn J Ophthalmol 2021 Sep 19;65(5):651-656. Epub 2021 Jun 19.

Kanazawa University, Kanazawa, Japan.

Purpose: The aim of this study was to elucidate the clinical features and symptoms of IgG4-related ophthalmic disease (IgG4-ROD).

Study Design: Retrospective, multicenter study.

Methods: The medical charts of 378 patients with IgG4-ROD diagnosed at 9 hospitals in Japan were reviewed. The demographic profiles, clinical findings, and ocular symptoms of the patients were analyzed.

Results: On the basis of the diagnostic criteria for IgG4-ROD, the diagnosis was definite in 261 patients (69%), probable in 45 patients (12%), and possible in 72 patients (19%). The patients' mean age at the time of diagnosis was 60.6 ± 13.9 years; 195 (52%) were male. The mean IgG4 serum level at the time of the initial diagnosis was 578.9 mg/dL. Imaging studies showed pathologic lesions as follows: lesions in the lacrimal glands (86%), extraocular muscles (21%), trigeminal nerve (20%), and eyelids (12%); isolated orbital mass (11%); diffuse orbital lesion (8%); lesion in the perioptic nerve (8%); and lesion in the sclera (1%). The ophthalmic symptoms included dry eye (22%), diplopia (20%), decreased vision (8%), and visual field defects (5%). IgG4-ROD with extraocular lesions was observed in 182 patients (48%).

Conclusion: Although the lacrimal glands are well known to be the major pathologic site of IgG4-ROD, various ocular tissues can be affected and cause ophthalmic symptoms including visual loss.
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http://dx.doi.org/10.1007/s10384-021-00847-3DOI Listing
September 2021

Association of Dry Eye Tests With Extraocular Signs Among 3514 Participants in the Sjögren's Syndrome International Registry.

Am J Ophthalmol 2016 Dec 16;172:87-93. Epub 2016 Sep 16.

Department of Orofacial Sciences, School of Dentistry, University of California San Francisco, San Francisco, California.

Purpose: To identify a screening strategy for dry eye patients with a high likelihood of having Sjogren syndrome (SS) through the evaluation of the association of ocular surface tests with the extraocular signs used for the diagnosis of SS.

Design: Multicenter cross-sectional study.

Methods: The Sjogren's International Clinical Collaborative Alliance (SICCA) registry enrolled 3514 participants with SS or possible SS from 9 international academic sites. Ocular surface evaluation included Schirmer I testing, tear breakup time (TBUT), and staining of the cornea (0-6 points) and conjunctiva (0-6 points). Multivariate logistic regression analysis was performed to identify predictive factors for (1) histopathologic changes on labial salivary gland (LSG) biopsies (positive = focus score of ≥1 focus/4 mm) and (2) positive anti-SSA/B serology.

Results: The adjusted odds of having a positive LSG biopsy were significantly higher among those with an abnormal Schirmer I test (adjusted OR = 1.26, 95% CI 1.05-1.51, P = .014) and positive conjunctival staining (for each additional unit of staining 1.46; 95% CI 1.39-1.53, P < .001) or corneal staining (for each additional unit of staining 1.14; 95% CI 1.08-1.21, P < .001). The odds of having a positive serology were significantly higher among those with an abnormal Schirmer I test (adjusted OR = 1.3; 95% CI 1.09-1.54, P = .004) and conjunctival staining (adjusted OR = 1.51; 95% CI 1.43-1.58, P < .001).

Conclusions: In addition to corneal staining, which was associated with a higher likelihood of having a positive LSG biopsy, conjunctival staining and abnormal Schirmer I testing are of critical importance to include when screening dry eye patients for possible SS, as they were associated with a higher likelihood of having a positive LSG biopsy and serology.
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http://dx.doi.org/10.1016/j.ajo.2016.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147490PMC
December 2016

An Adult Case of Fulminant Mumps Keratitis With Positive Viral RNA in Aqueous Humor Detected by RT-PCR.

Cornea 2016 Apr;35(4):569-71

Department of Ophthalmology, Kanazawa Medical University, Ishikawa, Japan.

Purpose: To report an adult case of mumps keratitis with mumps virus in aqueous humor and decreased corneal endothelial cell density.

Methods: Case report.

Results: A 60-year-old female with a 39°C fever and bilateral parotid swelling diagnosed with mumps and treated for photophobia, pain, redness, and decreased vision in 1 eye, was referred to our hospital when her condition deteriorated despite receiving betamethasone phosphate instillation and antiglaucoma agents for elevated intraocular pressure (52 mm Hg) and iritis. Her right eye was normal, whereas her left eye showed 20/400 visual acuity, 21 mm Hg intraocular pressure, ciliary injection and edema, opacity, and Descemet folds in the entire cornea. Round white keratic precipitates were present on the posterior corneal surface, whereas anterior chamber cells could not be examined in detail because of corneal edema. Mumps virus was detected by reverse transcriptase polymerase chain reaction in an aqueous humor sample taken at the time of admission. Following diagnosis of keratitis, administration of 30 mg oral prednisolone daily and frequent instillation of betamethasone phosphate steadily improved her corneal edema and opacity. In her left eye, visual acuity recovered to 20/16 and keratitis was resolved at 4 weeks; however, corneal endothelial cell density was significantly decreased to less than 400 per square millimeter.

Conclusions: Mumps keratitis may cause severe corneal endothelial cell loss.
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http://dx.doi.org/10.1097/ICO.0000000000000763DOI Listing
April 2016

Effect of rebamipide ophthalmic suspension on signs and symptoms of keratoconjunctivitis sicca in Sjögren syndrome patients with or without punctal occlusions.

Cornea 2014 Aug;33(8):806-11

Department of Ophthalmology, Kanazawa Medical University, Ishikawa, Japan.

Purpose: The aim of this study was to investigate the efficacy of 2% rebamipide suspension in treatment of keratoconjunctivitis sicca (KCS) in patients with Sjögren syndrome (SS) with or without punctal occlusions.

Methods: Thirty patients with SS, diagnosed based on the presence of autoantibodies and/or focus score >1 on lip biopsies, with corneal fluorescein staining scores (FSS) >3, and conjunctival lissamine green-staining scores (LSS) >3, were treated 4 times daily for 4 weeks with 2% rebamipide ocular suspension. Ocular examinations were performed before treatment and 2 and 4 weeks after treatment to evaluate FSS (0-9), LSS (0-6), and tear film break-up time (BUT). Hyaluronate and/or artificial tears were not discontinued. The patients were interviewed regarding the 5 major KCS symptoms, foreign body sensation, dry eye sensation, photophobia, ocular pain, and blurred vision, with each graded from none (0) to very severe (4).

Results: Of the 30 patients, 3 failed to attend all sessions, leaving 27 (25 females, 2 males, mean age 62.5 ± 10.8 years) to be studied. FSS and LSS showed improvement at week 2, but BUT showed improvement later, at week 4. All 5 symptoms improved significantly. When the patients were divided into 3 groups according to the presence of punctal occlusions, FSS and LSS were found to improve in all groups, but BUT improved only in patients with both puncta occluded at week 4.

Conclusions: Rebamipide ophthalmic suspension was effective in treating KCS of patients with SS, probably by increasing mucins and suppressing inflammatory cytokines. Punctal occlusions resulted in sufficient retention of tear fluid to enhance the activities of rebamipide and improve BUT.
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http://dx.doi.org/10.1097/ICO.0000000000000155DOI Listing
August 2014

Classification of secondary corneal amyloidosis and involvement of lactoferrin.

Ophthalmology 2013 Jun 28;120(6):1166-72. Epub 2013 Feb 28.

Ideta Eye Hospital, Kumamoto, Japan.

Purpose: To classify secondary corneal amyloidosis (SCA) by its clinical appearance, to analyze the demographics of the patients, and to determine the involvement of lactoferrin.

Design: Retrospective, observational, noncomparative, multicenter study.

Participants: Twenty-nine eyes of 29 patients diagnosed with SCA by corneal specialists at 9 ophthalmologic institutions in Japan were studied.

Methods: The clinical appearance of SCA was determined by slit-lamp biomicroscopy and was classified into 3 types. The demographics of the patients, for example, age, gender, and the duration of the basic disease (trichiasis, keratoconus, and unknown), were determined for each clinical type. Surgically excised tissues were stained with Congo red and antilactoferrin antibody. The postoperative prognosis also was determined.

Main Outcome Measures: Clinical appearance of the 3 types of SCA, along with the gender, age, and duration of the basic diseases were determined.

Results: Classification of SCA into 3 types based on clinical appearance found 21 cases with gelatinous drop-like dystrophy (GDLD)-like appearance (GDLD type), 3 cases with lattice corneal dystrophy (LCD)-like appearance (LCD type), and 5 cases with the combined type. Patients with the GDLD type were younger (average age: 40.9 years for the GDLD type, 74.3 years for the LCD type, and 46.8 years for the combined type), predominantly women (85.7% for the GDLD type, 33.3% for the LCD type, and 60% for the combined type), and had the basic disease over a longer time (average duration: 22.1 years for the GDLD type, 14.0 for the LCD type, and 11.4 for the combined type). The distribution of the basic diseases (trichiasis vs. keratoconus vs. unknown) was not significantly different for each type. Surgical treatments, for example, phototherapeutic keratectomy, lamellar keratoplasty, and simple keratectomy, resulted in a good resolution in all surgically treated cases. One subject dropped out of the study. Spontaneous resolution was seen in one subject after epilation of the cilia. Amorphous materials in the excised tissues showed positive staining results by Congo red and by antilactoferrin antibody.

Conclusions: Secondary corneal amyloidosis can be classified into 3 clinical types based on its clinical appearance. Larger numbers of females and lactoferrin expression were seen in all 3 types.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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http://dx.doi.org/10.1016/j.ophtha.2012.11.047DOI Listing
June 2013

A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjögren's Syndrome International Registry.

Am J Ophthalmol 2010 Mar 29;149(3):405-15. Epub 2009 Dec 29.

Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143-0422, USA.

Purpose: To describe, apply, and test a new ocular grading system for assessing keratoconjunctivitis sicca (KCS) using lissamine green and fluorescein.

Design: Prospective, observational, multicenter cohort study.

Methods: The National Institutes of Health-funded Sjögren's Syndrome International Registry (called Sjögren's International Collaborative Clinical Alliance [SICCA]) is developing standardized classification criteria for Sjögren syndrome (SS) and is creating a biospecimen bank for future research. Eight SICCA ophthalmologists developed a new quantitative ocular grading system (SICCA ocular staining score [OSS]), and we analyzed OSS distribution among the SICCA cohort and its association with other phenotypic characteristics of SS. The SICCA cohort includes participants ranging from possibly early SS to advanced disease. Procedures include sequenced unanesthetized Schirmer test, tear break-up time, ocular surface staining, and external eye examination at the slit lamp. Using statistical analyses and proportional Venn diagrams, we examined interrelationships between abnormal OSS (>or=3) and other characteristics of SS (labial salivary gland [LSG] biopsy with focal lymphocytic sialadenitis and focus score >1 positive anti-SS A antibodies, anti-SS B antibodies, or both).

Results: Among 1208 participants, we found strong associations between abnormal OSS, positive serologic results, and positive LSG focus scores (P < .0001). Analysis of the overlapping relationships of these 3 measures defined a large group of participants who had KCS without other components of SS, representing a clinical entity distinct from the KCS associated with SS.

Conclusions: This new method for assessing KCS will become the means for diagnosing the ocular component of SS in future classification criteria. We find 2 forms of KCS whose causes may differ.
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http://dx.doi.org/10.1016/j.ajo.2009.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459675PMC
March 2010

Dry eye and designer ophthalmics.

Optom Vis Sci 2008 Aug;85(8):643-52

Department of Cell Biology, University of Virginia, Charlottesville, VA, USA.

Expressed sequence tag (EST), proteomic, and antibody capture assays are revealing a level of tear film protein complexity far greater than previously appreciated. A systems biology approach will be needed to fully appreciate function as tear protein doses fluctuate in time through different conditions. Although consensus is growing on what fully constitutes the human tear proteome, questions remain about the source and significance of the approximately 256 tear proteins designated as "intracellular." Many of these may derive from normal cellular turnover and could therefore be informative. A further >183 are designated as "extracellular." Surprisingly, only 4 to 5% of these appear to be dysregulated in the three forms of dry eye preliminarily examined to date. Some differ and a couple overlap, suggesting that disease-specific signatures could be identified. Future dry eye treatment might include recombinant tear protein rescue as a personalized ophthalmic approach to ocular surface disease.
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http://dx.doi.org/10.1097/OPX.0b013e318181ae73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815326PMC
August 2008

[Comparison of minimum inhibitory concentration and postantibiotic effect of eyedrops on isolates in National Surveillance of Infectious Keratitis in Japan].

Nippon Ganka Gakkai Zasshi 2006 Dec;110(12):973-83

Department of Medical Technology, Osaka University Hospital. 2-15 Yamadaoka, Suita 565 0871, Japan.

Purpose: To determine the minimum inhibitory concentration (MIC) and postantibiotic effect (PAE) of antibiotic eyedrops against various isolates from infectious keratitis samples.

Method: MIC and postantibiotic bactericidal effect (PABE)/postantibiotic fungicidal effect (PAFE) after 4 min of exposure to nine antibacterial eyedrops or four antifungals were examined using 100 clinical isolates collected by the National Surveillance of Infectious Keratitis in Japan in 2003.

Result: The PABEs of tobramycin and micronomicin sulfate showed better results than other drugs, and the other drugs demonstrated various PABEs depending on the bacterial strains; in particular most drugs showed low PABE against Serratia marcescens. There were no significant differences between PABEs of methicillin-resistant and methicillin-susceptible Staphylococci. Also there was no statistical correlation between MIC and PABE of Staphylococci. All the antifungals demonstrated low PAFE against Candida spp.

Conclusion: PABE/PAFEs vary among species of microorganisms, and since they have no relation with the usual MIC, various other factors, including species of isolates, actual clinical effects, and prevention of drug-resistance induction, should be considered in the selection of drugs.
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December 2006

Prevalence and risk factors for cornea guttata in the Reykjavik Eye Study.

Ophthalmology 2006 Apr;113(4):565-9

Department of Ophthalmology, Landspitali University Hospital, Reykjavik, Iceland.

Purpose: To establish the age- and gender-specific prevalence of cornea guttata (CG) in citizens of Reykjavik, Iceland, 55 years and older.

Design: Cross-sectional, random, population-based study.

Participants: The 774 participants were those participating in the second examination of the Reykjavik Eye Study. At baseline, we had a response rate of 75.8%, and at the 5-year follow-up, 88% of the survivors participated.

Methods: We used slit-lamp and non-contact specular microscopy and endothelial specular photography as well as computer-assisted morphometry. We used a standardized grading system for CG.

Main Outcome Measures: Diagnosis of primary central CG.

Results: The prevalence of CG is 11% for females and 7% for males both for right eyes and left eyes. Higher weight and higher body mass index are found to be associated with decreased risk of CG. Having smoked more than 20 pack-years increased the risk of CG more than 2-fold (P<0.02).

Conclusions: Cornea guttata seem to be found more commonly in women than in men. Smoking for more than 20 pack-years increases the risk of developing CG more than 2-fold.
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http://dx.doi.org/10.1016/j.ophtha.2005.12.014DOI Listing
April 2006

Diagnostic potential of tear proteomic patterns in Sjögren's syndrome.

J Proteome Res 2005 May-Jun;4(3):820-5

Division of Nephrology, Department of Internal Medicine, Knanazawa Medical University, 920-0265 Ishikawa, Japan.

Histological and functional changes of the lacrimal gland might be reflected in proteomic patterns in tear fluids. In this study, we carried out a determination of the disease biomarkers in tear fluid for Sjögren's syndrome (SS) and a performance of noninvasive diagnostic test based on the proteomic patterns. Thirty-one SS patients and 57 control subjects were enrolled to this study. Their details were 23 cases with primary SS, 8 with secondary SS, 14 with dry eyes, 22 with miscellaneous ocular diseases, and 21 of healthy volunteers. Protein profiling in tear fluids was identified by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Multiple protein changes were reproducibly detected in the primary SS group, including 10 potential novel biomarkers. Seven of the biomarkers (2094, 2743, 14191, 14702, 16429, 17453, 17792 m/z) were down-regulated and 3 biomarkers (3483, 4972, 10860 m/z) were up-regulated in primary SS group, comparing to the protein profiles of control subjects. When cutoff value of SS down-score was set less than 0.5, this result yielded 87% sensitivity and 100% specificity. The positive predictive value for this sample set was 100%. There was a significant inverse correlation between SS down-scores and epithelial damages of the ocular surface in primary SS patients. These findings support the potential of proteomic pattern technology in tear fluids as the noninvasive diagnostic test for primary SS.
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http://dx.doi.org/10.1021/pr0497576DOI Listing
October 2005

Efficacy and retention rate of two types of silicone punctal plugs in patients with and without Sjögren syndrome.

Cornea 2004 Apr;23(3):249-54

Department of Ophthalmology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan.

Objective: To compare the efficacy, retention rates, and complications of two types of silicone lacrimal punctal plugs in patients with or without Sjögren syndrome.

Methods: We studied 36 patients with keratoconjunctivitis sicca (KCS) including 17 cases with Sjögren syndrome (SS) and 19 without SS. The fluorescein and rose bengal staining scores and the Schirmer values with and without nasal stimulation were evaluated before and after insertion of the Eagle Plugs and the punctal plugs (FCI Punctal Plugs). The retention rates and complications of these plugs were also investigated.

Results: The staining scores were significantly improved after the insertion of the plugs, but the Schirmer values did not increase significantly in either SS or non-SS patients. A spontaneous loss of the plugs was observed in 29% of all plugs within 1 month after insertion. The Eagle Plugs were lost more frequently, and plugs in the upper punctum were lost more often for the Eagle Plugs. There was one case of granulomatous proliferation and two cases of punctal infection with the FCI Punctal Plugs.

Conclusions: Both types of punctal plugs led to an improvement of the fluorescein and rose bengal staining scores in eyes with KCS. The difference in the retention rate and complications between the two types of plugs was probably caused by the differences in the material and the design of the plugs. Close monitoring is necessary to check for loss of plugs and to prevent complications.
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http://dx.doi.org/10.1097/00003226-200404000-00006DOI Listing
April 2004

[Two cases of primary biliary cirrhosis accompanied with severe keratoconjunctivitis sicca due to Sjögren syndrome].

Nippon Ganka Gakkai Zasshi 2003 Apr;107(4):219-25

Department of Ophthalmology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan.

Background: Primary biliary cirrhosis(PBC) is occasionally associated with Sjögren syndrome and results in liver cirrhosis. It occurs particularly in women, middle-aged or older, and is characterized by the presence of anti-mitochondrial antibody (AMA). We diagnosed PBC in 2 patients with severe keratoconjunctivitis sicca (KCS). CASE 1: A 45-year-old woman was diagnosed with PBC. A test for the presence of AMA was positive and liver dysfunction was detected. Tests for the presence of anti-SSA antibody and anti-SSB antibody were also positive. Signs of severe sicca syndrome observed in the oral cavity and in the eyes were compatible with signs of Sjögren syndrome. Furthermore, superior limbic keratoconjunctivitis was also observed. CASE 2: A 57-year-old woman was diagnosed with PBC and Sjögren syndrome. She also had thyroiditis and severe KCS. Tests for the presence of AMA, anti-SSA antibody, and anti-SSB antibody were positive. In both cases, eye drops were not effective as a treatment for the KCS, but lacrimal punctal occlusion with cauterization was effective.

Conclusion: PBC should be looked on as a disease that may possibly promote severe KCS.
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April 2003

The effect of nasal mucosal stimulation on Schirmer tests in Sjögren's syndrome and dry eye patients.

Adv Exp Med Biol 2002 ;506(Pt B):1221-6

Department of Ophthalmology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.

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http://dx.doi.org/10.1007/978-1-4615-0717-8_174DOI Listing
May 2003

Keratoconjunctitis sicca versus dry mouth and autoantibodies in primary and secondary Sjögren's syndrome.

Adv Exp Med Biol 2002 ;506(Pt B):1195-9

Department of Ophthalmology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.

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http://dx.doi.org/10.1007/978-1-4615-0717-8_169DOI Listing
May 2003

Successful management of conjunctival intraepithelial neoplasia by interferon alpha-2b.

Jpn J Ophthalmol 2002 Mar-Apr;46(2):215-7

Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.

Background: Interferon alpha-2b (IFN alpha 2b) was recently shown to be effective as an alternative therapy for conjunctival intraepithelial neoplasia (CIN). Herein, we report our successful management of CIN by the use of IFN alpha 2b.

Case: A 73-year-old woman presented with a complaint of irritation due to a tumorous lesion in her left eye. Slit-lamp microscope examination revealed a tumorous lesion involving the bulbar and palpebral conjunctiva as well as the limbus, from the 3-o'clock position to the 8-o'clock position. She had already undergone cryotherapy in the same eye in another hospital, twice for a lesion on the lower tarsal conjunctiva and once for a lesion on the upper tarsal conjunctiva. The histological diagnosis had been CIN.

Observations: In treating this patient, IFN alpha 2b was injected subconjunctivally twice and also applied as eye drops for 12 weeks. Two weeks after the initial treatment, the tumorous lesion disappeared. During a 1-year follow-up period, no recurrence was noted.

Conclusion: Topical and subconjunctival IFN alpha 2b is a valuable treatment option for CIN.
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http://dx.doi.org/10.1016/s0021-5155(01)00494-4DOI Listing
August 2002
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