Showing papers by "Kazuo Tsubota published in 2001"

Antiinflammatory effects of amniotic membrane transplantation in ocular surface disorders.

Abstract: Purpose.To determine whether the sequestration of inflammatory cells plays a role in the antiinflammatory effects of amniotic membrane transplantation to the ocular surface.Methods.Amniotic membrane grafts were prepared from placental tissue procured from mothers undergoing planned Cesarean sections

Dry eye after refractive surgery.

Abstract: Photorefractive keratectomy and laser in situ keratomileusis can induce or exacerbate dry eye after surgery. This manifests as an increase in degree and frequency of symptoms, corneal findings, such as superficial punctate keratopathy, and abnormal results of dry eye tests, such as the Schirmer test and tear break-up time. The cause mainly involves decreased corneal sensation, resulting in decreased feedback to the lacrimal gland and reduced tear production. Other causes may include increased evaporation, inflammation, or toxicity of medications. Dry eye may result infrequently in impaired wound healing and decreased optical quality of the cornea, but it is transient, lasting from a few weeks up to 1 year. Patients should be warned about this distressing complication. During a period of dry eye, artificial tears and punctal plugs are helpful in preventing or alleviating patient discomfort.

Treatment of superior limbic keratoconjunctivitis by application of autologous serum.

Abstract: Purpose.To determine the efficacy of autologous serum drops in the treatment of superior limbic keratoconjunctivitis (SLK).Methods.Twenty-two eyes of 11 patients were diagnosed with SLK. All eyes were treated with 20% diluted autologous serum eyedrops 10 times a day in addition to ongoing treatment

A significant role of stromal fibroblasts in rapidly progressive dry eye in patients with chronic GVHD.

Abstract: PURPOSE. To elucidate histopathologic features of the lacrimal gland in chronic graft-versus-host disease (GVHD) after alloge- neic hematopoietic stem cell transplantation. METHODS. Lacrimal gland specimens from five patients who had dry eye as part of the symptoms of chronic GVHD were examined by immunohistochemistry and transmission electron microscopy. Lacrimal gland specimens from five patients with Sjogren's syndrome (SS) were used as control samples. RESULTS. Lymphocytes, predominantly T cells, were found pri- marily in the periductal areas of the lacrimal gland from pa- tients with chronic GVHD, whereas B cells were the dominant infiltrating cells in the acinar areas of the lacrimal gland from patients with SS. Notable findings in the lacrimal gland from patients with chronic GVHD were marked fibrosis of the glan- dular interstitium and an increase in the number of CD34 1 stromal fibroblasts. These findings were more prominent in patients with severe dry eye than in those with mild dry eye. Electron microscopic observations of the lacrimal gland from patients with chronic GVHD revealed that stromal fibroblasts were attached to various inflammatory cells, especially T cells, through primitive or rudimentary contacts. In addition, the presence of a well-developed rough endoplasmic reticulum in the fibroblasts and newly synthesized collagen fibrils in the extracellular matrix indicated an active production of extracel- lular matrix components. Electron micrographs revealed mul- tilayered and thickened basal laminae of blood vessels, ducts, and lobules in the lacrimal gland of patients with chronic GVHD; however, these observations were infrequently ob- served in the lacrimal glands of patients with SS. CONCLUSIONS. The results suggest substantial differences in the lacrimal gland histopathology of patients with chronic GVHD and SS. In addition, it is likely that stromal fibroblasts are actively involved in the pathogenic process of chronic GVHD in the lacrimal gland by producing excessive extracellular ma- trix components. (Invest Ophthalmol Vis Sci. 2001;42: 111-119) D

Intact corneal epithelium is essential for the prevention of stromal haze after laser assisted in situ keratomileusis

Abstract: AIMS—To determine the effect of intact corneal epithelium on stromal haze and myofibroblast cell formation after excimer laser surgery. METHODS—Denuded epithelium alone, photorefractive keratectomy (PRK), laser in situ keratomileusis (LASIK), or LASIK with denuded epithelium was performed in rabbit eyes. Postoperative anterior stromal haze was assessed employing a standard scale. Immunohistochemical methods were used to detect alpha smooth muscle actin (α-SMA), a marker for myofibroblastic cells, and type III collagen in subepithelial corneal tissue. RESULTS—Three weeks after surgery, the presence of α-SMA positive long extended and spindle-shaped stromal cells, and synthesis of type III collagen were observed in the subepithelial stromal layer corresponding to corneal haze in PRK and LASIK with denuded epithelium, but not in denuded epithelium alone and LASIK. CONCLUSION—The intact corneal epithelium may play an important part curbing subepithelial haze and differentiation of myofibroblasts in corneal wound healing.

Ptyerygium and Dry Eye

Abstract: Purpose: To assess the correlation between dry eye and pterygium. Methods: Tear breakup time (BUT), Schirmer test with/without anesthesia and tear function index

Interleukin-8 concentrations in conjunctival epithelium brush cytology samples correlate with neutrophil, eosinophil infiltration, and corneal damage

Abstract: Purpose. To evaluate whether interleukin-8 (IL-8) and RANTES (regulated on activation, normal T-cell expressed and secreted) concentrations in the supernatants of conjunctival epithelial samples from patients with vernal keratoconjunctivitis (VKC) correlate with the number of infiltrating eosinophils or neutrophils and with the severity of corneal lesions. Methods. Thirty-four patients with VKC, 5 patients with seasonal allergic conjunctivitis, and 10 volunteers without allergic diseases were enrolled in this study. Conjunctival epithelial cells were collected by brush cytology and the number of inflammatory cells was counted. The chemokine expression in the cells was investigated by immunocytochemistry and the chemokine concentrations of the cell suspensions were measured by enzyme-linked immunosorbent assay. Results. The percentages of eosinophils and neutrophils in cell suspensions from VKC patients with corneal erosion or ulcer were higher than those from subjects with clear corneas or superficial punctate keratopathy. IL-8 concentrations in the supernatant of samples correlated significantly with the percentages of neutrophils and eosinophils in paired cell suspensions. No correlation was observed between RANTES and the percentages of eosinophils. Positive staining for IL-8 was observed in the cytosol of conjunctival epithelial cells. Conclusion. IL-8 in the extracellular space of the conjunctival epithelium may play a role in the recruitment of neutrophils and possibly eosinophils and in the pathogenesis of corneal damage in severe allergic diseases.

Successful treatment of dry eye in two patients with chronic graft-versus-host disease with systemic administration of FK506 and corticosteroids

Abstract: Purpose.We present two cases of severe dry eye in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (SCT) who were successfully treated by the systemic administration of FK506 and corticosteroids.Methods and Results.A 29-year-old man with chronic m

Effect of laser in situ keratomileusis correction on contrast visual acuity

Abstract: Purpose To evaluate the changes in contrast visual acuity (CVA) based on the amount of myopic correction with laser in situ keratomileusis (LASIK). Methods In this prospective study, patients with myopia ranging from –2.0 to –14.0 diopters (D) were divided into 2 groups: those with myopia less than –6.0 D (n = 20) and those with myopia greater than –6.0 D (n = 13). The CVA was measured preoperatively and 1 week and 1 and 3 months postoperatively using Variable Contrast Visual Acuity Charts. Results The patients with less than –6.0 D of myopia had a CVA decrease of 15% 1 week postoperatively, which recovered by 1 month, and a decrease of 2.5% 1 week and 1 month postoperatively, which recovered by 3 months. The patients with more than –6.0 D of myopia had a decrease of 15% and 2.5% at all postoperative times. Conclusions After LASIK to correct myopia of greater than –6.0 D, there may be a persistent decrease in intermediate and low CVA. Patients should be informed preoperatively of this possible decrease in CVA.

Lack of evidence for an increased microchimerism in the circulation of patients with Sjögren's syndrome

Abstract: Objective—To examine the hypothesis that fetal microchimerism plays a part in the pathogenic process of Sjogren’s syndrome (SS). Methods—Genomic DNA samples were extracted from peripheral blood whole nucleated cells and the CD34+ cell enriched fraction of patients with SS and healthy women who had male oVspring as well as nulliparous women. A Y chromosome-specific sequence was detected as a marker for fetal cells by a nested polymerase chain reaction (PCR) and by DNA hybridisation combined with PCR using specific primers and probes. All procedures were performed with great care to avoid the contamination of male DNA. Results—A nested PCR and DNA hybridisation combined with PCR was established that can detect a single male cell out of 1.67×10 5 female cells. It was not possible to increase the sensitivity further because the amount of template DNA held in the PCR was limited. When these methods were used, no fetal cells were detected in any samples from patients with SS, though they were detected in whole nucleated cells from two healthy women who had delivered sons previously. Conclusions—The findings indicate that circulating fetal cells in patients with SS are uncommon (<1 in 1.67×10 5 ), if they exist. With the conventional PCR based methods that were used, it is diYcult to evaluate the quantitative diVerence in circulating fetal cells between patients with SS and healthy women. (Ann Rheum Dis 2001;60:248‐253)

Immunologic rejection of the central graft after limbal allograft transplantation combined with penetrating keratoplasty.

Abstract: PURPOSE To study the incidence and prognosis of immunologic rejection of the central graft after limbal allograft transplantation (keratolimbal allograft transplantation [KLAT]) combined with penetrating keratoplasty (PKP). METHODS Endothelial rejection in central penetrating graft after simultaneous KLAT and PKP using the same donor cornea was retrospectively studied. Incidence, reversibility, prognosis, and changes in limbal grafts were examined. RESULTS Forty-five eyes underwent simultaneous PKP and KLAT. Endothelial rejection of the central graft was found in 16 eyes (35.6%). At last examination, 10 grafts (62.5%) restored clarity after immunosuppressive therapy. During rejection episodes, four eyes showed engorgement of vessels in limbal grafts, which existed before the episodes. Only one eye developed neovascularization with mild edema of the limbal grafts; however, no other limbal grafts showed abnormalities on biomicroscopy. No epithelial changes were noted, and 14 grafts (87.5%) were covered by corneal epithelium after the rejection. CONCLUSION Approximately one third of eyes had endothelial rejection in the central graft after simultaneous KLAT and PKP. Abnormalities suggestive of rejection in the limbal grafts were seldom observed in these eyes, suggesting that immunologic response was different in central and limbal grafts.

Possible involvement of EBV-mediated alpha-fodrin cleavage for organ-specific autoantigen in Sjogren's syndrome.

Abstract: A cleavage product of alpha-fodrin may be an important organ-specific autoantigen in the pathogenesis of Sjogren's syndrome (SS), but the mechanisms of alpha-fodrin cleavage remain unclear Since EBV has been implicated in the pathogenesis of SS, we determined whether EBV activation could induce the SS-specific 120-kDa autoantigen alpha-fodrin ZEBRA mRNA expression, a marker for activation of the lytic cycle of EBV, was found in the salivary gland tissues from SS patients, but not in those from control individuals ZEBRA-expressing lymphoid cells were also found in the SS glands in double-stained immunohistochemistry Furthermore, a significant link between production of Abs against 120-kDa alpha-fodrin and reactivated EBV Ag was found in sera from patients with SS, but not in those from control individuals EBV-activated lymphoid cells showed specific alpha-fodrin cleavage to the expected 120-kDa fragments in vitro Pretreatment with caspase inhibitors inhibited cleavage of alpha-fodrin Thus, an increase in apoptotic protease activities induced by EBV reactivation may be involved in the progression of alpha-fodrin proteolysis in the development of SS

Improvement of Lacrimal Function by Topical Application of CyA in Murine Models of Sjögren’s Syndrome

Abstract: Purpose The object of this study was to evaluate improvement of lacrimal gland (LG) function after topical cyclosporin A (CyA) Methods Topical CyA (001% and 01%) was applied to two mouse models of Sjogren's syndrome, the NFS/sld after thymectomy and the nonobese diabetic (NOD) mouse, and the functional integrity of the lacrimal gland was evaluated by measuring basal and stimulated tear secretion and its histologic integrity by examining it for apoptosis and lymphocyte invasion Results After treatment with CyA at 01% in the NFS/sld mice, tear function increased, and there was a decrease in lymphocyte infiltration of the LG and a decrease in apoptotic figures among the acinar cells In the NOD mice, tear function also improved, but there was no associated decrease in lymphocyte infiltration However, the expression of Fas ligand (FasL) in NOD mice by infiltrating lymphocytes was suppressed with 0 1% CyA eye drops Conclusions CyA appears to improve tear secretion in mouse models of Sjogren's syndrome by preventing lymphocyte-induced apoptosis of acinar cells In one model this was achieved by preventing lymphocyte infiltration and in the other by reducing expression of FasL expression on infiltrating lymphocytes

Quantitative evaluation of atopic blepharitis by scoring of eyelid conditions and measuring the water content of the skin and evaporation from the eyelid surface.

Abstract: PURPOSE To quantitatively evaluate the condition of the eyelid skin of patients with atopic blepharitis, their symptoms were scored and the water content of the skin and evaporation from the skin were measured. METHODS Forty patients with atopic blepharitis were examined. The condition of eyelid skin (erythema, edema/papulation/oozing/crust, excoriation/lichenification) was scored from 0 to 3 points. Water content and water evaporation were measured with a Moisture Checker and an evaporimeter, respectively. Eleven age-matched volunteers without atopic disorders were recruited as normal controls. RESULTS The Moisture Checker values and water evaporation from lid skin were significantly correlated (r = -0.44, p = 0.006). The Moisture Checker values of the patients with atopic blepharitis was 35.5+/-8.2% (44.7 +/-10.6% in the normal controls, p = 0.009), and water evaporation from their lid skin was 3.6+/-0.9 g/cm2 per second (2.0+/-0.3 g/cm2 per second, p < 0.001); then, the patients were divided into four groups, from "asymptomatic" to "severe," according to the sum of their blepharitis scores. Patients with lower blepharitis scores tended to have higher Moisture Checker values and lower water evaporation values. CONCLUSION Scoring of eyelid condition enabled us to objectively estimate the severity of atopic blepharitis. Measurements of the water content of lid skin and water evaporation from lid skin are useful in evaluation of the severity of this disease.

Suppressive effect of locally produced interleukin-10 on respiratory syncytial virus infection.

Abstract: Interleukin (IL)-10 is known to be a multifunctional cytokine. This study was designed to evaluate the role of IL-10 during respiratory syncytial virus (RSV) infection using a C57BL/6 transgenic (TG) mouse model in which the expression of murine IL-10 cDNA was regulated by a human salivary amylase promoter (IL-10 TG mice). These mice expressed a large amount of IL-10 in the nasal mucosa and in salivary glands. Viral replication in the respiratory tract after intranasal infection with RSV was suppressed significantly in IL-10 TG mice compared to non-transgenic controls. This suppression was IL-10 specific, because it was prevented by treating mice with neutralizing anti-IL-10 antibodies. We also found that IL-10-stimulated T cells displayed cytotoxic activity against infected murine nasal epithelial cells. Previous data indicated that IL-10 induces Fas ligand (L) expression on mouse T cells. Taken together, these data suggest that Fas/Fas L mediated cytotoxicity is involved in the suppression of RSV replication observed in IL-10 TG mice after intranasal infection.

Allergic conjunctivitis as a risk factor for laser in situ keratomileusis

Abstract: Purpose: To analyze the effect of allergic conjunctivitis (AC) on the outcome of laser in situ keratomileusis (LASIK) in myopic eyes. Setting: Minamiaoyama Eye Clinic, Tokyo, Japan. Methods: Patients who had LASIK were divided into 2 groups: those with AC (84 eyes of 49 patients; the allergic group) and those without AC (140 eyes of 77 patients; the nonallergic group). Allergic conjunctivitis was diagnosed clinically by symptoms of eye itching and clinical findings such as papillary proliferation on the tarsal conjunctiva. Preoperative and postoperative uncorrected visual acuity (UCVA) and refraction and intraoperative and postoperative complications were compared. Results: There were no significant differences in UCVA and refraction between the 2 groups. No complications were observed in the allergic group. Intraoperative conjunctival chemosis (3 eyes of 2 patients) and a postoperative epithelial defect that resulted in epithelial ingrowth (1 eye) were observed in the nonallergic group. Conclusion: The findings suggest that AC is not a risk factor for LASIK.