HLA class II DNA typing using ocular tissue and its usefulness in corneal transplantation.
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Cornea↗
Biomedical subjects
K Tsubota
Publications and source records attributed to K Tsubota.
[A case of Sjögren's syndrome with an eyelid tumor, a so-termed pseudolymphoma of the iacrimal gland].
The female subject, 64 years old, subjectively noticed a mild dryness of the eyes and bilateral, submandibular swelling in 1988. The clinical symptom was mild, and such autoantibody and hyper-gammaglobulinemia as often observed in Sjögren's syndrome were not recognized. However, by judging from the results of gum test (9 mL/10 min), salivary gland scan (Grade 2) and the labial biopsy, we diagnosed the case as Sjögren's syndrome. We then administered prednisolone at 40 mg at the onset of treatment and gradually decreasing the dosage over 3.5 years, and the symptoms improved. As an eyelid tumor in the left eye was noticed in 1991 and began to enlarge, the subject was hospitalized in June of 1992. The biopsy of the tumor (2.0 x 1.7 cm) showed marked polyclonal lymphoproliferation with lymphoid follicles which was determined by immunohistological staining. The case was a patient with a lymphoproliferative lesion from a lacrimal gland which is equal to a so-termed pseudolymphoma. Since there are some reports concerning the transition from pseudolymphoma to malignant lymphoma, this patient should be followed carefully.
Eyelid Neoplasms↗
Biopsy of labial salivary glands and lacrimal glands in the diagnosis of Sjögren's syndrome.
OBJECTIVE: To determine the diagnostic value in Sjögren's syndrome (SS) of evaluating the presence of focal adenitis in labial salivary gland (LSG) and lacrimal gland (LG) biopsy specimens. METHODS: We studied 105 cases with suspected SS and performed biopsies prospectively. The diagnostic criteria of Fox, et al were followed. The Chisholm-Mason grading standard and Greenspan focus score were used for evaluation. RESULTS: Epimyoepithelial islands and severe lymphocyte infiltration with germinal centers were observed only in LG biopsy specimens (5.9 and 3.5%, respectively). The lymphocytic focus scores of LG (2.5 +/- 2.1/4 mm2) were significantly higher than those of LSG specimens (1.3 +/- 1.1/4 mm2) in 23 cases with both biopsy results (p < 0.05). Six of the 32 LSG biopsies were normal while their LG biopsies were significantly higher. Conversely, 5 of the 32 LG biopsies were aided by corresponding LSG biopsies, since in LG biopsies no glandular tissue was obtained. Evaluation of both specimens for the same patient was significantly more effective in diagnosing SS than using either specimen alone (p < 0.01). CONCLUSION: LG biopsy specimens have a more evident histopathology than LSG biopsy specimens. We recommend that both LSG and LG biopsies be performed in patients with suspected SS to reduce false negative results and improve diagnostic accuracy.
Biopsy↗
Decreased reflex tearing is associated with lymphocytic infiltration in lacrimal glands.
OBJECTIVE: To investigate whether reflex tearing measured by the Schirmer test with nasal stimulation is better correlated with lymphocytic infiltration of the lacrimal gland and is thus a more appropriate test for Sjögren's syndrome (SS). METHODS: 272 patients with dry eye (age 55.5 +/- 13.5 years) with regular Schirmer test results < 10 mm were recruited for the study. They were divided into 2 groups depending on the results of the Schirmer test with nasal stimulation. 24 age and sex matched patients from each group were selected for lacrimal gland biopsy and 10 patients for salivary gland biopsy, and the levels of systemic autoantibodies and degrees of ocular surface staining and lymphocytic infiltration of the lacrimal and salivary glands were compared. RESULTS: Of the 272 patients, 187 (68.8%) had good reflex tearing (GT) and 85 (31.2%) had poor reflex tearing (PT). There were no significant differences in the age or sex of the 2 groups. Lymphocytic infiltration of the lacrimal gland was observed in 7 GT cases and 22 PT cases out of 24 cases. Lymphocytic infiltration of the salivary gland was also higher in the PT (6 of 10) than the GT group (2 of 10). CONCLUSION: Evaluation of reflex tearing by the Schirmer test with nasal stimulation identifies 2 groups of patients with dry eye. Those with poor reflex tearing were more likely to have autoantibodies and lymphocytic infiltration of the exocrine glands consistent with SS.
Adult↗
Limbal autograft transplantation for recurrent and advanced pterygia.
BACKGROUND AND OBJECTIVE: This study was conducted to examine the usefulness of limbal autograft transplantation in the treatment of recurrent and advanced pterygia. PATIENTS AND METHODS: Eleven patients with recurrent and 16 with advanced pterygia (a total of 27 pterygia) were treated with limbal autograft transplantation. Once a pterygium had been excised, superior limbal tissue was taken with conjunctival flap and transferred to the excised area. RESULTS: All the grafts were planted promptly, and donor sites were re-epithelialized with no excessive scar tissue formation. Although slight recurrence was noted in 2 eyes (7.4%), subconjunctival tissue invasions were limited to less than 1 mm, and no further surgical interventions were needed. CONCLUSION: These results indicate that limbal autograft transplantation may be effective for the treatment of recurrent and advanced pterygia.
Adult↗
Tear function index. A new measure of dry eye.
OBJECTIVE: To develop an efficient way to evaluate tear dynamics clinically. PARTICIPANTS: Three hundred fifty-two patients with dry eye, 64 of whom had Sjögren syndrome, and 55 normal subjects. DESIGN: Because various forces that affect tear drainage are reflected in the values of the Schirmer test with anesthesia and the tear clearance rate, we introduced a new measure of tear dynamics, the tear function index, which is the value obtained from dividing the value of the Schirmer test with anesthesia by the tear clearance rate. RESULTS: The tear function index was more specific (91.8%) and sensitive (78.9%) in diagnosing dry eye associated with Sjögren syndrome than was the Schirmer or tear clearance rate test alone. Tear function indexes below 96 were consistent with dry eye and those below 34 were seen primarily in patients with Sjögren syndrome. CONCLUSIONS: The tear function index offers a new method to evaluate tear production with the Schirmer test, introduces an extended way to measure tear flow combining with tear drainage, and gives a practical measure to diagnose dry eye.
Dry Eye Syndromes↗
Effects of ocular surface area and blink rate on tear dynamics.
OBJECTIVE: To study the effects of exposed ocular surface area and blink rate on tear dynamics by the measurement of tear evaporation under a range of conditions. METHODS: Tear evaporation was measured in three gaze positions in 15 normal volunteers, and the ocular surface area was determined as a function of the width of the palpebral fissure. In 17 normal volunteers, the effect of blink rate on tear evaporation was assessed. RESULTS: The ocular surface area was 1.2 +/- 0.27, 2.2 +/- 0.39, and 3.0 +/- 0.33 cm2 with patients looking down, ahead, and up, respectively. The corresponding tear evaporation rates per eye were 7.0 +/- 3.5, 17.6 +/- 6.6, and 23.7 +/- 6.3 x 10(-7) g/s, respectively. The tear evaporation per square meter also increased proportionally with the ocular surface area. When the blink rate was changed from 10 to 60 per minute, the tear evaporation did not change in those individuals with evaporation rates more than 7.8 x 10(-7) g/s per square centimeter, whereas it did increase with the blink rate in those whose evaporation rates were lower. CONCLUSIONS: Ocular surface area and blink rate affect tear dynamics. Moderate palpebral fissure width and blink rate are necessary for the prevention of desiccation of the ocular surface.
Adult↗
Ocular surface changes and discomfort in patients with meibomian gland dysfunction.
OBJECTIVE: To determine the importance of meibomian gland dysfunction (MGD) on the ocular surface. DESIGN: Prospective study. SETTING: A university-based referral practice. PATIENTS: Patients with ocular discomfort (147 eyes) and without ocular discomfort (54 eyes) were examined. In the total 201 eyes, MGD was defined as the presence of an obstruction of the meibomian orifices (obstruction group [n = 54]) or the absence of a gland structure (gland dropout group [n = 36]), or both of these findings (combined group [n = 38]). There were not any findings of MGD in 73 eyes (non-MGD group). MAIN OUTCOME MEASURES: Scores that were obtained from fluorescein and rose bengal staining, the breakup time of the tear film, the rates of tear evaporation and tear production, and meibography. RESULTS: Of the 147 eyes with ocular discomfort, 95 (64.6%) had either an obstruction of an orifice or gland dropout, or both. The combined group had higher scores for staining with fluorescein (P = .002) and rose bengal (P = .021) compared with that in the non-MGD group. The rate of tear production was increased more in the gland dropout group than in the non-MGD group (P = .002). The rate of tear evaporation was significantly increased in the gland dropout group (P = .017). CONCLUSION: Meibomian gland dysfunction is a major cause of ocular surface abnormalities and ocular discomfort.
Adult↗
Reversal of abnormal corneal epithelial cell morphologic characteristics and reduced corneal sensitivity in diabetic patients by aldose reductase inhibitor, CT-112.
PURPOSE: A randomized clinical study was undertaken to determine whether a topically applied aldose reductase inhibitor, CT-112, was capable of reversing the abnormal morphologic characteristics of corneal epithelial cells, as well as the reduced corneal sensitivity, in diabetic patients. METHODS: Thirty-nine diabetic patients were randomly divided into two groups: one group was treated with topical aldose reductase inhibitor (CT-112) in an ophthalmic preparation, and a control group was treated with the same preparation without the inhibitor. Specular microscopy was performed to analyze the morphologic characteristics of corneal epithelial cells before and after the treatment. Corneal sensitivity was measured by means of the Cochet-Bonnet esthesiometer. RESULTS: The anterior surface area of superficial cells in the group treated with CT-112 was significantly decreased from a mean value of 881 to 728 microns2 (P < .0001), whereas the control group showed no significant changes. Corneal sensitivity remained decreased in the control group, whereas that in the group treated with CT-112 significantly improved, from 5.36 to 1.37 g/mm2 (P < .0001). CONCLUSIONS: These results indicate that treatment with topical CT-112 is capable of reversing abnormal morphologic characteristics of corneal epithelial cells and reduced corneal sensitivity in diabetic patients.
Aged↗
Increased comfort and decreased inflammation of the eye by cooling after cataract surgery.
PURPOSE: Cooling can reduce clinical symptoms and pain caused by traumatic swelling or fracture of extremities. We obtained subjective and objective measures of the effects of cooling of the eyes after cataract surgery. METHODS: Twenty patients with bilateral cataracts were enrolled in this study. For each patient, an ice-cold eye mask was applied over gauze to one operated-on eye for two hours after the operation and was not applied after operation on the other eye. After each operation, the patient rated comfort on a five-point scale. The severity of inflammation associated with each procedure was evaluated by using an infrared radiation thermometer to determine the central corneal temperature and a laser flare-cell meter to determine the cell and flare count, at intervals up to 28 days after surgery. RESULTS: Cooling, applied after the first operation in ten patients and after the second operation in ten patients, statistically significantly increased the patients' comfort level and was associated with a significant decrease in central corneal temperature on days 0, 1, and 3; in cell counts on days 1, 3, 7, and 14; and in flare counts on days 1, 14, and 28. CONCLUSIONS: Cooling increased the comfort level and reduced inflammation after cataract surgery, with no adverse effects.
Aged↗
Respiratory syncytial virus and allergic conjunctivitis.
The pathogenesis of allergic conjunctivitis is largely conjectural. We investigated the possible involvement of respiratory syncytial virus (RSV), a ubiquitous respiratory pathogen, in the development of allergic conjunctivitis through immune mechanisms. A new technique of brush cytology was used to obtain conjunctival cells from 30 patients with allergic conjunctivitis and 20 control subjects. Samples were assayed for the presence of RSV sequences with the reverse-transcription polymerase chain reaction and the nested polymerase chain reaction. Specific primers and inner primers were synthesized on the basis of RNA sequences previously identified. RSV sequences were detected in 7 of 30 (23%) patient samples and 1 of 20 (5%) control samples. Our results proved that polymerase chain reaction could detect RSV sequences in conjunctival samples. RSV may be a significant pathogenic factor in allergic conjunctivitis.
Adolescent↗
Reconstruction of the corneal epithelium by limbal allograft transplantation for severe ocular surface disorders.
PURPOSE: Although penetrating keratoplasty is an established surgical procedure, it often is ineffective for severe ocular surface diseases such as alkali burns or limbal deficiency. The authors have performed limbal allograft transplantation for the reconstruction of the corneal epithelium. METHODS: A total of nine patients (3 with chemical injury, 3 with limbal deficiency with unknown etiology, 2 with moderate ocular pemphigoid [OCP], and 1 with traumatic limbal deficiency) were treated by limbal allograft transplantation. Penetrating keratoplasties were performed in all patients with the exception of one with OCP. Patients received cyclosporine both systemically (10 mg/kg) and topically (0.05%) as well as high-dose intravenous dexamethasone (8 mg). RESULTS: The corneal epithelium was reconstructed in all patients, although two showed partial increased fluorescein permeability and two others required a second surgery. The other five epithelia remained clear at mean follow-up of 12.3 months, with two episodes of graft rejection which were controlled successfully by medication. CONCLUSIONS: Limbal allograft transplantation with intensive immunosuppression by cyclosporine and high-dose steroids appears to be a promising surgical intervention for the reconstruction of corneas affected by severe ocular surface disease.
Adult↗
Dry eye with only decreased tear break-up time is sometimes associated with allergic conjunctivitis.
PURPOSE: The authors' clinical experience has suggested that there is a form of dry eye with only decreased tear break-up time, which is associated with allergic conjunctivitis. The current study was performed to verify this hypothesis. METHOD: The authors recruited patients with two types of dry eye syndrome, those with only decreased tear break-up (BUT type) and those with positive vital staining (staining type). Individuals without any symptoms or signs served as controls. All subjects were compared regarding symptoms, Schirmer and tear clearance test results, conjunctival papillary formation, antigen-specific serum-IgE level (s-IgE), and goblet cell density of the palpebral conjunctiva. Antigen-induced allergic conjunctivitis was produced in guinea pigs, and histopathologic changes of the conjunctiva were examined. RESULTS: Patients with the BUT-type dry eye syndrome were younger and their symptoms were as severe as the staining type. The Schirmer and tear clearance test results were better, and the papillary formation and s-IgE were observed more than in the BUT type. The average goblet cell density in the BUT-type syndrome was 625.4 +/- 193.2/mm2, which was significantly less than 1005.6 +/- 294.5/mm2 in the controls (P < 0.01). The average goblet cell density was significantly decreased in the allergic animals (10.40 +/- 1.11/0.2 mm) compared with that of the controls (16.21 +/- 0.26/0.2 mm) or the anti-allergic drug-treated group (13.69 +/- 0.30/0.2 mm) (P < 0.01). CONCLUSION: These results support the authors' hypothesis that decreased break-up time is in part associated with the decreased goblet cell density caused by allergic conjunctivitis.
Adult↗
Long-term follow-up of patients with familial subepithelial amyloidosis of the cornea.
PURPOSE: To investigate the clinical course of patients with familial subepithelial amyloidosis of the cornea (FSA). METHODS: The authors retrospectively investigated the clinical course of seven Japanese patients with FSA. Corneal specimens obtained at the time of keratoplasty were examined histopathologically. RESULTS: The mean follow-up period was 20.6 years, including four patients followed for more than 25 years. In all patients, the initial symptoms of photophobia and epiphora started in the first decade of life. All except one patient had their first keratoplasty before 30 years of age. The seven Japanese patients with FSA had a total of 35 keratoplasties, each of which was followed by a severe recurrence of disease. In each patient, subepithelial haziness developed in the graft within 1 year of keratoplasty (mean, 7.9 months). Amyloid deposition typically recurred within a few years (mean, 26.6 months) followed by a deterioration of vision. There was a high incidence of postkeratoplasty complications such as wound dehiscence, glaucoma, and cataract. Histopathologic findings demonstrated that, in the early phase of recurrence, amyloid was deposited between the basal cell of the epithelium and Bowman's layer. CONCLUSION: Patients with FSA have ocular symptoms with a deterioration in vision from an early decade of life. Conventional surgical approaches were complicated by subepithelial haziness in the first postoperative year, which was followed by a severe recurrence in each patient. New surgical approaches may be indicated in FSA.
Adult↗
Diverse T cell receptor beta gene usage by infiltrating T cells in the lacrimal glands of Sjögren's syndrome.
Sjögren's syndrome (SS) is an autoimmune disease characterized by T cell infiltration into the salivary and lacrimal glands (LG). Previous studies on T cell receptor (TCR) usage in the minor salivary glands (SG) have yielded controversial results. We studied TCR beta gene usage of the T cells infiltrating to LG, which is the other major target organ of SS. Total RNA was extracted from fresh LG and SG biopsy samples, and peripheral blood mononuclear cells from five SS patients, and converted to cDNA. TCR V beta gene repertoire was then assessed with quantitative polymerase chain reaction (PCR) assay. Oligoclonality was studied by sequencing V-D-J junctional regions of the PCR products. The TCR V beta gene usage in LG was diverse in every patient irrespective of disease duration, and similar to that of peripheral lymphocytes from a corresponding patient. The junctional region sequences of over-expressed V beta families in LG T cells were heterogeneous. We did not find any identical clones shared by LG, SG and peripheral blood. These results showed that the infiltrating T cells in LG of SS patients are polyclonal, and LG and SG do not share the same dominant T cell clonotypes. These suggest that TCR-targeted disease manipulation may have a limited effect on SS.
Aged↗
Measurement of IL-4 in tears of patients with seasonal allergic conjunctivitis and vernal keratoconjunctivitis.
To elucidate the mechanism of ocular surface allergic disease, we focused on IL-4, which is one of the key factors in regulating IgE production, and thus determined the concentration of IL-4 in tears. IL-4 concentration was determined in the tears of 15 patients with seasonal allergic conjunctivitis, 15 vernal keratoconjunctivitis (VKC), 10 giant papillary conjunctivitis (GPC), 10 patients with non-allergic conjunctivitis and post-cataract surgical conjunctivitis as intermediate conjunctivitis, and 10 normal subjects using a highly sensitive sandwich ELISA. The mean level of IL-4 in normal controls was low, and seasonal allergic conjunctivitis, VKC and GPC showed a significant elevation (P < 0.05), respectively. IL-4 of VKC and GPC were also significantly higher than allergic conjunctivitis, and non-allergic conjunctivitis and post-cataract surgical conjunctivitis were not higher than normal. These results raise the possibility that the increased level of IL-4 in tears could play a role in allergic disease and its severity in patients.
Adolescent↗
Increased levels of Epstein-Barr virus DNA in lacrimal glands of Sjögren's syndrome patients.
Many Sjögren's syndrome patients complain primarily of dry eye. Epstein-Barr virus DNA has recently been found in the lacrimal glands of Sjögren's syndrome sufferers and normal individuals, and lacrimal glands are thought to be a target organ for latent Epstein-Barr virus infection. In this study, we performed lacrimal and salivary gland biopsies on 9 Sjögren's syndrome patients. Extracted Epstein-Barr virus DNA was assayed by polymerase chain reaction and compared to that of healthy individuals. An increased level of Epstein-Barr virus DNA was observed in all of the lacrimal glands and 8 of the 9 salivary glands from the Sjögren's syndrome patients. However, the amount of genome in the lacrimal gland was more than 10 times that in the salivary glands, not only in the Sjögren's syndrome patients but also in the controls. This may explain the pathogenesis of dry eye in patients with Sjögren's syndrome, and why the lacrimal gland tends to be so prominently affected. It may also suggest a therapeutic approach for this and possibly other types of dry eye.
Base Sequence↗
Effect of occlusion on human skin.
In order to investigate the effect of occlusion on the skin, the flexor sides of both upper arms were covered with column-shaped with column-shaped closed chambers, 30 mm in outer diameter, 20 mm in inner diameter, and 5 mm in height, which were made of polyethylene foam. The tops of the chambers were sealed by plastic films with various levels of water vapor permeability to control moisture in each chamber. The raised chamber walls prevented direct contact between the skin and the plastic film. After 24 h of application, morphological changes of the skin surface were observed microscopically by the nitrocellulose-replica method. Although no visual alterations were found on all areas of occluded skin, microscopic evaluation showed that simple occlusion by films induced an increase in the number of deepened skin furrows on the skin surface. this increase was associated with lower water vapor permeability of the films, as well as with higher values of both temperature and humidity of the test day. Thus, since conditions which facilitate perspiration from the skin tend to cause skin irritation, prolonged exposure of the skin to sweat by simple occlusion may act as a primary skin irritant.
Adult↗