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Biomedical subjects

K Tsubota

Publications and source records attributed to K Tsubota.

At least 73 records · Page 4Linked to original sources

Iatrogenic cataract after laser-assisted in situ keratomileusis.

PURPOSE: To report a case of corneal opacity and iatrogenic cataract after laser-assisted in situ keratomileusis. METHOD: Case report. A 44-year-old man was initially seen with a traumatic cataract, corneal stromal opacity, and defect of the endothelium in the right eye after laser-assisted in situ keratomileusis performed by a plastic surgeon who had no ophthalmologic training. RESULTS: It was speculated that repeated ablations resulted in corneal perforation. We immediately performed phacoemulisification to remove the cataract and to prevent phacolytic glaucoma. However, visual acuity remained 20/200 because of the corneal stromal opacity, and penetrating keratoplasty was performed 2 months later, which improved best-corrected visual acuity to 20/30. CONCLUSIONS: This case demonstrated that laser-assisted in situ keratomileusis can cause devastating damage to the eye.

Adult↗

Surgical treatment of children blinded by Stevens-Johnson syndrome.

PURPOSE: The surgical treatment of severe Stevens-Johnson syndrome is considered to be very difficult, especially in children. However, ocular surface reconstruction is possible in certain cases. METHODS: We have performed ocular surface reconstruction by allogeneic corneal epithelial stem cell transplantation in four children blinded by Stevens-Johnson syndrome. RESULTS: Two cases failed, and the other two had excellent results. The successful cases had good lacrimal function and conjunctival epithelium, with clear corneal stroma and pathology limited to the superficial ocular tissue, whereas the failures did not. CONCLUSIONS: The successful ocular surface reconstruction has been stable for more than 1 year in two cases, suggesting that some patients with Stevens-Johnson syndrome are very good candidates for ocular surface reconstruction, especially when the patients have good tear function and healthy conjunctival epithelium.

Amnion↗

Treatment of persistent corneal epithelial defect by autologous serum application.

OBJECTIVE: To evaluate the efficacy of autologous serum application for the treatment of persistent epithelial defect. DESIGN: Prospective, clinical, noncomparative case series. PARTICIPANTS: A total of 16 eyes were studied. INTERVENTION: Autologous serum was prepared from the patients and diluted to 20% by saline. The patients were instructed to use the autologous serum six to ten times a day. The concentration of vitamin A, epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta) was measured at 1 week and 1 month stored in the refrigerator and 1 month and 3 months in the freezer. MAIN OUTCOME MEASURES: Time to closure of epithelial defect. RESULTS: Vitamin A, EGF, and TGF-beta were stable during the 1 month in the refrigerator and 3 months in the freezer. Among 16 persistent epithelial defects, 7 (43.8%) healed within 2 weeks, 3 (18.8%) healed within 1 month, and the remaining 6 (37.5%) did not respond within 1 month. No apparent side effect of autologous serum application was observed. CONCLUSIONS: Autologous serum application healed 43.8% of persistent defect within 2 weeks and 62.5% within 1 month.

Adult↗

Thermal effect on corneal incisions with different phacoemulsification ultrasonic tips.

PURPOSE: To evaluate the thermal effects of 3 phacoemulsification ultrasound (US) tips (standard, MicroTip, and Mackool) on the corneal incision based on the tip's position. SETTING: Department of Ophthalmology, Tokyo Dental College, Tokyo, Japan. METHODS: Thermal changes were recorded with an infrared thermal video during phacoemulsification in 18 porcine eyes. The 3 US tips were placed in 3 positions (primary, roofing, and flanking) in the corneal incision, and the resultant temperature changes were recorded. RESULTS: With the 3 US tips in the primary position, the temperature remained under 36 degrees C. When the tips were in the roofing position, a marked temperature increase (51.4 degrees C) was observed with the standard tip; with the MicroTip, a temperature increase occurred but was lower than with the standard tip; with the Mackool tip, the temperature remained stable. The temperature around the incision site increased with all tips when they were moved toward the corner of the incision, which resulted in direct contact with the silicone sleeve. This change was most obvious with the standard tip (temperature 51.5 degrees C), and a wound burn was observed. With the MicroTip, the temperature increase was moderate (44.2 degrees C), and the wound burn area was smaller. With the Mackool tip, the temperature increased the least (42.1 degrees C). CONCLUSION: The position of the US tips resulted in a temperature increase in the incision area and caused wound burn. Newly developed US tips could minimize this complication.

Animals↗

Efficacy and safety of infrared warming of the eyelids.

PURPOSE: To evaluate our newly developed infrared heater (IRH) and compare it to a broad-spectrum heater (BSH) for warming the eyelids. MATERIALS AND METHODS: Ten normal subjects were enrolled in this study. All measurements were recorded in a room with temperature 23 degrees C, 40% humidity, and no wind. The IRH is composed of two hard eye patches that have light-emitting diodes (LEDs) emitting near-infrared radiation. We first compared the temperature rises in the cornea, lacrimal gland, and eyelids after warming through closed eyelids with the IRH for 5 and 10 min. Next, we compared warming with the IRH or BSH for 30 min. We then used the IRH for 5 min with the eyes open to confirm its safety. Finally, we determined subjective feeling after warming the eyes. RESULTS: Direct comparison of 5 versus 10 min of warming with the IRH showed no significant differences in temperature rises in the upper eyelid (p = 0.09). The IRH caused significantly more heating (p < 0.05) than did the BSH everywhere except the cornea. The temperatures never rose above 37.7 degrees C for either heater during 30 min or with the IRH with the eyes open for 5 min. The subjects' comfort level rose significantly (p < 0.05) after treatment with the IRH. CONCLUSIONS: Our study showed the efficacy and safety of warming the eyelids with a newly developed IRH. Only 5 min is necessary to increase ocular temperature and enhance comfort.

Adult↗

Results of a population-based questionnaire on the symptoms and lifestyles associated with dry eye.

PURPOSE: This study was designed to assess public awareness and symptoms of dry eye in Japan by a population-based, self-diagnosis study. METHODS: Two thousand five hundred participants chosen randomly from the general population were sent a questionnaire consisting of 30 questions pertaining to symptoms and knowledge of dry eye. RESULTS: Awareness of the condition called "dry eye" was very high at 73%. Most of the knowledge of dry eye was obtained through the media (e.g., television, 58.8%; newspapers/magazines, 46.6%), and only a fraction of the knowledge was from physicians (6.8%). As many as 33% of participants responded that they believed they had dry eye according to the self-diagnosis criteria, of which 25% used over-the-counter eyedrops daily. The majority of eyedrop users were dissatisfied with their therapeutic effects, and only 11% sought professional help. Habits in lifestyles that were associated with self-diagnosed dry eye were contact lens use (p < 0.001), a history of allergic conjunctivitis (p = 0.002), and video display terminal tasks (p = 0.058). CONCLUSION: Although public awareness of dry eye in Japan was high, only a minority of the population seems to consult professionals for diagnosis and symptomatic relief.

Adult↗

Diseases associated with ocular surface abnormalities: the importance of reflex tearing.

AIM: To investigate the correlation between tear function tests and ocular surface integrity in patients with dry eye. METHODS: 297 dry eye patients (55 Sjögren's syndrome, two male and 53 female, average age 52.4 (SD 15.0) years, and 242 non-Sjögren's syndrome, 41 male and 201 female, average age 53.5 (14.1) years) were examined. The following tear function tests were performed: (1) cotton thread test, (2) Schirmer test with topical anaesthesia, (3) Schirmer test without anaesthesia, (4) Schirmer test with nasal stimulation, (5) tear clearance test, and (6) tear break up time (BUT). The ocular surface was evaluated by rose bengal and fluorescein staining. Correlation analysis was performed between each tear function index and vital staining scores. RESULTS: Among the six tear function tests, the Schirmer test with nasal stimulation correlated most with both of the vital stains (rho = 0.530 for rose bengal and 0.393 for fluorescein). The Schirmer test with or without anaesthesia correlated slightly with rose bengal staining, whereas tear clearance test and tear break up time slightly correlated with fluorescein staining. CONCLUSION: Vital staining of the ocular surface correlates most with reflex tearing measured by the Schirmer test with nasal stimulation.

Dry Eye Syndromes↗

Dry eye after haematopoietic stem cell transplantation.

AIMS: To determine the incidence, natural course, and severity of dry eye occurring or worsening after haematopoietic stem cell transplantation (SCT). METHODS: At a tertiary care hospital, 53 patients undergoing allogeneic or autologous SCT followed by at least 180 days of follow up were studied prospectively. Examination included grading of symptoms of dry eye, evaluation of ocular surface, tear break up time, and Schirmer tests with and without nasal stimulation. Meibomian gland secretion was also examined using a slit lamp while applying steady digital pressure. RESULTS: Of the 53 patients, 44 received allografts. Half of these patients (22) developed dry eye or their pre-existing dry eye worsened after SCT, while none of nine autograft recipients did. Onset of dry eye was 171 (SD 59) days after SCT. Two types of dry eye occurred. One (n=10) was severe with ocular surface findings resembling Sjögren's syndrome and reduction of reflex tearing soon after onset. A mild type (n=12) had unimpaired reflex tearing. Meibomian gland dysfunction (MGD) was more frequent and severe in patients with dry eye and chronic graft versus host disease (GVHD), and overall severity of dry eye was greater in patients with MGD and chronic GVHD. CONCLUSIONS: Dry eye after SCT occurred only in allograft recipients, and was not evident in autograft recipients. The severe form of dry eye had a tendency to develop rapidly. Further study on the prediction and treatment of severe dry eye after SCT is necessary.

Adult↗

Treatment of dry eye by autologous serum application in Sjögren's syndrome.

AIM: To evaluate the efficacy of autologous serum application for the treatment of dry eye in Sjögren's syndrome. METHODS: The stability of essential components (EGF, vitamin A, and TGF-beta) in preserved serum were examined following preservation at 4 degrees C and -20 degrees C. In a primary clinical trial, 12 patients with Sjögren's syndrome were treated with autologous serum (diluted to 20% with sterile saline) for 4 weeks, and vital staining of the ocular surface was compared before and after treatment. The effects of serum on mucin (MUC-1) expression were observed in cultured conjunctival epithelial cells in vitro. RESULTS: EGF, vitamin A, and TGF-beta were well preserved for up to 1 month in the refrigerator at 4 degrees C and up to 3 months in the freezer at -20 degrees C. Rose bengal and fluorescein scores improved significantly from the initial scores of 5.3 and 5.6 to 1.7 and 2.5 after 4 weeks, respectively. The additive effect of human serum for cultured conjunctival epithelial cells showed significant MUC-1 upregulation on the cell surface. CONCLUSION: Autologous serum application is a safe and efficient way to provide essential components to the ocular surface in the treatment of dry eye associated with Sjögren's syndrome.

Blood↗

New treatment of dry eye: the effect of calcium ointment through eyelid skin delivery.

AIM: To demonstrate the efficacy of a petrolatum based calcium ointment applied to the lower lid skin in the management of dry eye. METHODS: In a controlled double masked study, the effects of water free petrolatum ointment containing calcium carbonate (10% w/w) on tear functional factors and ocular surface vital staining in dry eye patients were observed. Petrolatum without calcium carbonate served as control. Patients were instructed to place ointment to the lower lid skin twice a day. Evaluation of subjective complaints, fluorescein and rose bengal staining patterns, blink rate, tear evaporation and tear break up time (BUT) were performed before and 3 months after treatment. In order to demonstrate the movement of petrolatum from the skin to the tear film, petrolatum containing 1% sodium fluorescein was placed on the lower lid of four healthy volunteers, and the concentration of fluorescein in the tear film was followed up to 6 hours using an anterior fluorometer. RESULTS: Subjective symptoms significantly improved in both the calcium group (p=0.001) and control (p=0.012), while only the calcium group demonstrated a significant improvement in fluorescein (p=0.043), rose bengal (p=0.021) scores, and blink rate (p=0.004). Tear evaporation also significantly decreased in both the calcium group (p=0.0004) and control (0.043). BUT did not improve in either group. CONCLUSION: Petrolatum based calcium ointment significantly improved symptoms, tear dynamics, and ocular surface staining in dry eye patients. However, some of the therapeutic effects may be due to lipids in the petrolatum vehicle. Petrolatum applied to the lower lid skin is an effective drug delivery system for slowly releasing drugs to the ocular surface.

Administration, Cutaneous↗

IL-4 regulates chemokine production induced by TNF-alpha in keratocytes and corneal epithelial cells.

BACKGROUND: Eosinophils are thought to play a major role in the pathogenesis of corneal lesions in ocular allergies. The regulation of chemokine production in corneal cells by the Th2 cytokine, interleukin 4 (IL-4), was examined in order to investigate its role in ocular allergies. METHODS: Pure cultures of human corneal epithelial cells and keratocytes were exposed to tumour necrosis factor alpha (TNF-alpha) and/or IL-4. 24 hours after exposure, culture supernatants were removed and concentrations of IL-8 and RANTES were quantified by ELISA assay. RESULTS: Simultaneous addition of IL-4 inhibited TNF-alpha induced IL-8 production in both corneal epithelial cells and keratocytes. TNF-alpha and IL-4 synergistically stimulated the production of RANTES in keratocytes. CONCLUSION: Differential regulation of chemokine production from corneal cells by IL-4 may play a role in the selective recruitment of predominantly eosinophils to the ocular surface in ocular allergies.

Cells, Cultured↗

Conjunctival epithelium expression of HLA-DR in dry eye patients.

PURPOSE: To compare conjunctival epithelium expression of HLA-DR and ICAM-1 with tear dynamics and ocular surface parameters. METHODS: Brush cytology and flow cytometry were used to quantitatively analyze HLA-DR and ICAM-1 expression in 28 dry eye patients. RESULTS: HLA-DR was expressed in 66% of the conjunctival cells of dry eye patients. This expression correlates with that of ICAM-1, as well as with the Schirmer test results (p < 0.05). CONCLUSION: This study confirmed that dry eye consists not only of ocular surface desiccation, but also of upregulation of the HLA-DR and ICAM-1 molecule in the conjunctival epithelium, possibly resulting in increased inflammation.

Antibodies, Monoclonal↗

Excimer laser-induced hydroxyl radical formation and keratocyte death in vitro.

PURPOSE: To characterize the type of reactive oxygen species (ROS) produced by excimer photoablation of aqueous solutions and to show the effects of ROS and antioxidants on corneal stromal cells in vitro. METHODS: Electron spin-resonance spectroscopy was performed using the spin-trapping agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO) for the detection of the superoxide anion and the hydroxyl radical in an acellular DMPO solution irradiated with the excimer laser. Hydroxyl radicals were produced by the Fenton reaction in vitro by the mixture of hydrogen peroxide and ferrous iron (Fe2+), and the effects on cultured corneal fibroblasts were observed by fluorescent microscopy using the cell death marker, propidium iodide (PI) and TdT-mediated dUTP nick-end labeling (TUNEL). RESULTS: Excimer photoablation of a 1% DMPO solution produced a species-specific spin-trapping adduct for the hydroxyl radical ('OH), but not for the superoxide anion or other unidentified free radical. The signals were inhibited dose dependently by the hydroxyl radical scavenger dimethylsulfoxide (DMSO) and an L-ascorbic acid analogue, EPCK-1. The production of *OH in the supernatant of cultured rabbit corneal fibroblasts by the Fenton reaction caused an increase in PI (+) and TUNEL (+) cells by 90 minutes, which was significantly inhibited by the addition of DMSO. CONCLUSIONS: Hydroxyl radicals may be partly responsible for stromal fibroblast cell apoptosis after excimer photoablation.

Animals↗

Evidence of long-term survival of donor-derived cells after limbal allograft transplantation.

PURPOSE: Severe destruction of the corneal limbus causes conjunctival invasion and subsequent visual loss. Limbal allograft transplantation (LAT) was recently proposed for the treatment of these disorders. However, whether the method functions as a stem cell transplantation of the corneal epithelium remains unclear. This study provided evidence that donor-derived corneal epithelial cells survive long after LAT. METHODS: Epithelial cells on the paracentral cornea in patients who have undergone LAT were subjected to fluorescence in situ hybridization (FISH) and polymerase chain reaction restriction fragment length polymorphism (RFLP) analysis. X and Y chromosomes were detected using sex chromosome-specific probes in the FISH analysis, and HLA-DPBI antigens were examined in the RFLP analysis. Eyes receiving conventional penetrating keratoplasty (PKP) served as controls. RESULTS: Donor-derived epithelial cells were detected in three of five eyes (60.0%) in the FISH analysis and in seven of nine eyes (77.8%) in the RFLP analysis. Among these eyes, one and three eyes in the FISH and RFLP analysis, respectively, had both donor- and recipient-derived cells. In control PKP eyes, none of the eyes in the FISH analysis and one of eight eyes (12.5%) in the RFLP analysis had donor-derived cells. CONCLUSIONS: These results suggest that donor-derived cells survive much longer after LAT than those after PKP, and that LAT may function as stem cell transplantation of the corneal epithelium.

Adolescent↗

Morphology and barrier function of the corneal epithelium after penetrating keratoplasty: association with original diseases, tear function, and suture removal.

PURPOSE: To study changes in structure and barrier function of the corneal epithelium after penetrating keratoplasty. METHODS: Sixty-nine eyes of 56 patients undergoing penetrating keratoplasty were studied. Fifty-six age-matched normal eyes served as controls. Corneal epithelial structure was studied by using specular microscopy. Barrier function of the corneal epithelium was examined by slit-lamp fluorophotometry. Vital staining, tear function, and corneal sensitivity also were examined. RESULTS: Fluorescein and rose bengal staining scores, incidence of elongated cells, the mean epithelial area, and mean fluorescein uptake were significantly increased in postkeratoplasty eyes compared with controls. Original disease influenced the results of barrier function, where keratoconus revealed better function than bullous keratopathy or corneal scar. However, no such differences were noted in epithelial structure. Six eyes with absence of palisades of Vogt had revealed significantly increased epithelial area and fluorescein uptake. Removal of the running suture caused a decrease in elongated cells and epithelial cell area without significant changes in barrier function. CONCLUSION: Corneal epithelial structure was significantly impaired in postkeratoplasty eyes. Epithelial barrier function of postkeratoplasty eyes was influenced by original diseases. Removal of sutures improves epithelial structure but not barrier function.

Adolescent↗

The impact of HLA-A matching in corneal transplantation.

Previously, we have reported the results of our retrospective study on the effect of HLA class II allele matching on the outcome of corneal transplant. Here, we demonstrate our findings of the study for HLA class I allele matching in the same study subjects. Eighty transplant recipients were typed for HLA-A, and 79 transplant recipients were typed for HLA-B alleles, by PCR-SSOP. The association between HLA class I allele matching and 1-year rejection-free graft survival was evaluated. When a total of 79 transplant recipients were subdivided into groups with matching (one to four alleles matched) and without matching (no allele matched) for HLA class I (HLA-A and -B), a significantly higher rate of 1-year rejection-free graft survival was detected in transplant recipients with matching, compared with those without matching (p=0.0258). We have found that matching for at least one HLA class I allele was more beneficial especially in high-risk transplant recipients (p=0.0076). Also, an analysis of matching for each locus separately, detected that, HLA-A matching was significantly associated with a higher rate of 1-year rejection-free graft survival. Transplant recipients with HLA-A matching (one or two-alleles matched) had significantly higher rejection-free graft survival compared with those without matching (no allele matched), when high- and low-risk groups were analyzed together (p=0.0099). Furthermore, matching for HLA-A allele was significantly beneficial compared with no matching in high-risk transplant recipients (p=0.0154). Nevertheless, no significant effect of HLA-B matching was detected. We conclude that HLA class I, especially HLA-A matching has a beneficial effect for corneal transplant outcome.

Alleles↗

Regulation of human leukocyte antigen expression in human conjunctival epithelium.

PURPOSE: To demonstrate that interferon-gamma (IFN-gamma) is the key cytokine responsible for the upregulation of HLA-DR antigen in conjunctival epithelial cells of Sjogren syndrome (SS) patients. METHODS: Flow cytometry of conjunctival epithelial cells from SS and non-SS dry eye patients was performed for the quantification of HLA-DR surface expression. With a conjunctival epithelial cell line (ChWK), HLA-DR regulation by various cytokines was evaluated, and confocal immunocytochemical and western blot analyses were performed to evaluate the activation of nuclear factorkappa B (NF-kappaB) and signal transducers and activators of transcription 1 and 3 (STAT1 and STAT3, respectively). RESULTS: HLA-DR expression was upregulated in conjunctival epithelial cells of SS patients but not in non-SS dry eye patient or healthy control subject. IFN-gamma was the only cytokine that effectively upregulated HLA-DR expression in ChWK, which was synergistically enhanced by tumor necrosis factor-alpha (TNF-alpha). IFN-gamma induced the nuclear translocation of NF-kappaB, but did not activate STAT1 or STAT3 in ChWK. CONCLUSIONS: Upregulation of HLA-DR antigen in the conjunctival epithelium of SS patients may be regulated by IFN-gamma through the activation of NF-kappaB.

Adult↗