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Biomedical subjects

Kazuo Tsubota

Publications and source records attributed to Kazuo Tsubota.

At least 19 recordsLinked to original sources
PubMed2003

Visualization of gaseous monoxide reception by soluble guanylate cyclase in the rat retina.

Immunohistochemistry using novel monoclonal antibodies (mAbs) allowed us to uncover tissue activities of soluble guanylate cyclase (sGC) fine tuned by NO and CO. Upon NO and CO applications in vitro, purified sGC increased the affinity to mAb3221 by 100- and 10-fold, respectively, but not to mAb28131. Immunohistochemistry for gas-generating enzymes revealed that NO occurred in amacrine, bipolar, and Müller's glia cells (MGCs), whereas CO was derived mostly from heme oxygenase (HO)-2 in MGCs. Basal sGC immunoreactivities in vivo to mAb3221 but not to mAb28131 were enhanced by injecting L-arginine and attenuated by blocking NO synthases, suggesting the ability of the former mAb to sense NO. Comparison of mAb-assisted immunohistochemistry suggested that sGC activities were enhanced by zinc protoporphyrin-IX, an HO inhibitor, and repressed completely by blocking NO. However, suggested roles of CO played in situ varied among different retinal layers. In inner plexiform and inner nuclear layers located in the proximity of the cellular NO sources, CO serves as a simple inhibitor of local sGC, while playing roles in housekeeping sGC activation in external limiting membrane standing far from them. These results suggest that CO generated in MGCs is a diffusible gas mediator regulating sGC in both autocrine and paracrine manners.

Animals↗
PubMed2003

Improved functional visual acuity after punctal occlusion in dry eye patients.

PURPOSE: To report an increased functional visual acuity, which was recently reported as a simulation of visual function of daily acts of gazing, in dry eye patients after punctal occlusion. DESIGN: Prospective comparative interventional study. METHODS: We measured ordinary best-corrected visual acuity and functional visual acuity in eight eyes of eight dry eye patients after punctal occlusion, and compared the results with those of 22 eyes of 22 dry eye patients without punctal occlusion. RESULTS: Functional visual acuity in dry eye patients after punctal occlusion was 0.962 in decimal notation, which was significantly higher than that of patients without punctal occlusion, 0.283 (P <.0001). CONCLUSIONS: This study shows that punctal occlusion can improve the impaired functional visual acuity of dry eye patients.

Dry Eye Syndromes↗
PubMed2003

Lecithin-bound superoxide dismutase in the treatment of noninfectious corneal ulcers.

PURPOSE: To evaluate the effects of a lipophilic analog of superoxide dismutase in the treatment of persistent epithelial defects of the cornea. DESIGN: Interventional case series. METHODS: Nineteen eyes of 19 patients with noninfectious corneal ulcers were enrolled. Patient profiles consisted of seven cases with Mooren-type peripheral ulcers, three cases with chemical or thermal burns, two cases with vernal keratoconjunctivitis, four cases with cicatricial keratoconjunctivitis, and three cases with sterile ulcers after corneal surgery. Patients consisted of 11 men and 8 women, with a mean age of 51.5 +/- 17.9 years (range, 14-77). Only patients who did not respond to conventional therapy were recruited for the study. Lecithinated superoxide dismutase was applied for 2 weeks, and sketches and/or fluorescein slit micrographs were recorded before and at the end of the study. The main outcome measure was decrease in ulcer size. RESULTS: As a group, the average ulcer size relative to the entire cornea decreased from 18.2 +/- 15.1% to 10.0 +/- 15.0% after 2 weeks (P <.05). A dramatic effect (>90% decrease in ulcer size) was observed in eight cases (100% in six cases), whereas no apparent change was found (<30% decrease in ulcer size) in five cases. The presence of polymorphonucleocytes within the ulcerated tissue was confirmed by brush cytology. CONCLUSION: Lecinthinated superoxide dismutase was effective in decreasing persistent epithelial defect size in a subset of patients with sterile corneal ulcers refractive to conventional therapy. A large-scale clinical investigation is merited.

Adolescent↗
PubMed2003

Therapeutic deep lamellar keratoplasty for cornea perforation.

PURPOSE: To present the efficacy of performing deep lamellar keratoplasty as an emergency measure following perforation of the cornea. DESIGN: Interventional case report. METHOD: Deep lamellar keratoplasty was performed in two cases of perforated cornea. Following incarceration of the iris within the perforated area, The Descemet membrane was exposed except for strands of stroma surrounding the perforation. A fresh donor cornea stripped of the Descemet membrane was then sutured in place. RESULTS: Both cases have attained clear corneas in areas other than the original perforation. CONCLUSIONS: Deep lamellar keratoplasty is a safe technique for the treatment of cornea perforation.

Adolescent↗
PubMed2003

A new method for tear film stability analysis using videokeratography.

PURPOSE: To report a new tear film stability analysis system using videokeratography. DESIGN: Observational case series. METHODS: New videokeratography software for TMS-2N (topographic modeling system; TOMEY Corporation, Nagoya, Japan) was developed that can automatically capture consecutive corneal surface images every second for 10 seconds. Forty-eight adult volunteers (80 eyes) were recruited for this study, and all subjects were examined with the new system. Corneal topographs were analyzed for tear breakup time (TMS-BUT) and the ratio of breakup area to entire color-code area (TMS-BUA) was calculated. Routine methods for tear film breakup time evaluation using slit-lamp microscope and fluorescence staining (SLE-BUT) were performed for comparison purposes. Regressive correlations of TMS-BUT or TMS-BUA with SLE-BUT were analyzed. Based on SLE results, subjects were separated into two groups with normal and short BUT, respectively. TMS-BUT and TMS-BUA were compared with SLE-BUT data with regard to the sensitivity and specificity of evaluation of dry eye symptoms. RESULTS: Topographic modeling system-tear breakup time (TMS-BUT) had a positive correlation with SLE-BUT (R = 0.7219, P <.0001), whereas TMS-BUA showed a negative correlation (R = 0.6317, P <.0001). Among 34 eyes with normal SLE-BUT, 11 eyes (32.35%) displayed abnormal TMS-BUT, 9 (81.82%) of which were associated with dry eye symptoms. The sensitivities of TMS-BUT and TMS-BUA were 97.5% and 95%, respectively, significantly higher than that of SLE-BUT (75%), with P =.008 and 0.01, respectively. Topographic modeling system-BUT and TMS-BUA displayed a similar rate of specificity in comparison with SLE-BUT. CONCLUSIONS: This new videokeratography system is a noninvasive and objective method with increased sensitivity for tear film stability analysis.

Adolescent↗
PubMed2003

Abnormal protein profiles in tears with dry eye syndrome.

PURPOSE: To verify the hypothesis that protein concentrations, such as lactoferrin, epidermal growth factor (EGF), and aquaporin 5 (AQP5), in tears are abnormal in patients with dry eye. DESIGN: Prospective case-control study. METHODS: One hundred three dry eye patients were divided into three groups: dry eye not associated with the Sjögren syndrome (non-SS; n = 71), Sjögren syndrome (SS; n = 23), and Stevens-Johnson syndrome (SJS; n = 9). Sixteen normal control subjects were also checked. The concentrations of lactoerrin, EGF, and AQP5 were measured by enzyme-linked immunosorbent assay. RESULTS: The concentration of lactoferrin was significantly decreased in tears of non-SS (P =.0001), SS (P =.00005), and SJS (P =.0006) patients compared with control subjects. The concentration of EGF was significantly decreased in non-SS (P =.0005), SS (P =.00002), and SJS (P =.0001) patients compared with control subjects. The concentration of AQP5 was significantly increased in tears of only SS patients (P =.01) compared with control subjects and increased in tears of only SS patients compared with non-SS patients (P =.007). CONCLUSIONS: The decrease in both lactoferrin and EGF was found not only in SS patients but also in non-SS patients, indicating that tear components in dry eyes differ in their quantity and quality. Quantification of AQP5 increased only in SS patients, suggesting that AQP5 protein leaks into the tears when acinar cells of the lacrimal gland are damaged by lymphocytic infiltration.

Adolescent↗
PubMed2003

Quantitative analysis of lacrimal gland function, apoptotic figures, Fas and Fas ligand expression of lacrimal glands in dry eye patients.

The purpose of our study was to examine the correlation between the lacrimal gland function and apoptotic figure, Fas and Fas ligand (FasL) expression in the lacrimal gland. A total of 15 dry eye patients (nine Sjögren's syndrome and six non-Sjögren's syndrome-type dry eye) were recruited for the study. Lacrimal function was evaluated by Schirmer tests 1 and 2. Lacrimal gland biopsies were performed and sections were analyzed by immunohistochemistry using APO2.7, an antibody to Fas and FasL. Quantitative analysis of fluorescein staining was performed by a scanning laser microscopy. Schirmer test 2 results were lower in Sjögren's syndrome-type dry eye and were associated with positive staining of acinar cells with APO2.7 and of infiltrating lymphocytes with FasL. There was a good correlation between the results of Schirmer test 2 and APO2.7 and FasL staining. Lacrimal gland dysfunction is related to the apoptotic figure of acinar cells possibly induced by FasL on the infiltrating lymphocytes.

Adult↗
PubMed2003

Amniotic membrane transplantation with conjunctival autograft for recurrent pterygium.

OBJECTIVE: To study the effect of amniotic membrane transplantation (AMT) combined with either limbal autograft transplantation (LAT) or conjunctival autograft transplantation (CAT) in recurrent pterygium. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty-seven eyes of 27 patients with recurrent pterygium. The mean number of prior surgeries was 3.1 (range, 1-10). Fifteen eyes each had restriction of ocular movement and symblepharon before surgery. INTERVENTION: Patients were treated by AMT with either LAT (n = 15) or CAT (n = 12). MAIN OUTCOME MEASURES: Recurrence of pterygium, improvement in ocular movement, and symblepharon formation. RESULTS: Twenty-three (85.2%) of 27 eyes showed no recurrence with a mean observation period of 67.0 weeks. Fourteen eyes (93.3%) each showed improvement in ocular movement restriction and symblepharon after AMT. In four eyes that developed recurrence, three had LAT and one had CAT combined with AMT, suggesting that there was no difference in surgical outcome between LAT and CAT. CONCLUSIONS: AMT with CAT is a safe and effective method for recurrent pterygium, especially that associated with ocular movement restriction and symblepharon. Considering the potential adverse effects associated with limbal excision, AMT plus CAT may be preferred over AMT plus LAT.

Adolescent↗
PubMed2003

Tear function and ocular surface changes in keratoconus.

PURPOSE: To describe the ocular surface disorder in patients with keratoconus. DESIGN: A prospective, case-controlled study. PARTICIPANTS: Seventy-five eyes of 38 patients with keratoconus seen at Uludag University School of Medicine, Department of Ophthalmology, from March 2000 through April 2001, and 80 eyes of 40 normal control subjects were studied. INTERVENTION: The subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, Schirmer test, tear film breakup time (BUT), fluorescein and rose bengal staining of the ocular surface, and conjunctival impression cytology. MAIN OUTCOME MEASURES: Patients and control subjects were compared for corneal sensitivity, tear function, ocular surface staining parameters, goblet cell density, and squamous metaplasia grade. The relation of these parameters to the severity of keratoconus progression was also investigated. RESULTS: The mean corneal sensitivity was significantly lower in keratoconus patients compared with control subjects (P < 0.001). The BUT values were also significantly lower in the keratoconus group. Patients with keratoconus had significantly higher fluorescein and rose bengal staining scores (P < 0.001). Corneal sensitivity and tear function changes seemed to get worse with advanced stages of keratoconus. Impression cytology showed goblet cell loss and conjunctival squamous metaplasia, both of which again related to the extent of progression of keratoconus. CONCLUSIONS: The ocular surface disease in keratoconus is characterized by disorder of tear quality, squamous metaplasia, and goblet cell loss, all of which seem to relate to the extent of keratoconus progression.

Adolescent↗
PubMed2003

Corneal opacity and cataract: triple procedure versus secondary approach.

PURPOSE: To determine the efficacy of planned secondary cataract surgery after keratoplasty. METHODS: Twenty patients (22 eyes) with simultaneous corneal pathology and cataract were enrolled in a prospective, interventional, case-matched, nonrandomized comparative trial. Penetrating keratoplasty (PKP) and extracapsular cataract extraction (ECCE) with IOL insertion (triple procedure) were performed in 11 eyes, and planned phacoemulsification (PEA) with IOL insertion after PKP was performed in 11 case-matched eyes. RESULTS: There were 10 eyes (91%) within +/-2.0 D of expected values in the secondary PEA group versus 5 patients (45%) in the triple procedure group. No difference was observed in endothelial cell density after 1-year follow-up. CONCLUSIONS: Planning for secondary PEA in PKP patients with cataracts is a safe and reliable procedure to obtain less post surgical refractive error. Performing a two-stage intervention has no effect on corneal endothelial viability after 1 year.

Adult↗
PubMed2003

Tear evaporation dynamics in normal subjects and subjects with obstructive meibomian gland dysfunction.

PURPOSE: To test a newly developed tear evaporimetry system that detects real-time changes in tear evaporation rates and shows the tear film stability in patients with obstructive meibomian gland dysfunction (MGD). METHODS: A ventilated chamber system with high-sensitivity microbalance sensor was used to evaluate tear evaporation. Tear evaporation rates and dynamic changes in them in response to blinking ("flip heights") were measured. Both were compared in 38 eyes of 22 normal subjects and 32 eyes of 21 patients with obstructive MGD, in a prospective case-control study. The relationship between tear evaporation rates and flip heights to meibomian gland orifice obstruction was also analyzed. RESULTS: Changes in tear evaporation rates produced by blinking were detected. The tear evaporation rates in the patients' group were 5.8 +/- 2.7(10(-7)) g/cm(2) per second, significantly higher than in normal subjects (4.1 +/- 1.4[10(-7)] g/cm(2) per second; P = 0.0008). The flip heights in the obstructive MGD group were 0.58 +/- 0.33(10(-7)) g/cm(2) per second, significantly higher than in normal subjects (0.39 +/- 0.27[10(-7)] g/cm(2) per second, P = 0.02). The correlations between both tear evaporation rates and flip heights to the meibomian gland orifice obstruction score were statistically significant (P < 0.0001 and P = 0.004, respectively). CONCLUSIONS: This new system was helpful in differentiating MGD patients from normal subjects. These significantly higher evaporation rates and higher flip heights reflect the unstable tear evaporation and may well indicate unstable tear film in patients with obstructive MGD with abnormal evaporative tear loss.

Adult↗
PubMed2003

[Regeneration of the cornea].

The cornea is a transparent, colorless tissue that functions as the optical surface of the eye. Transparency is vital for useful vision, which can be compromised by disorders to the corneal epithelium, stroma or endothelium. Transplantation of donor corneas is the standard surgical procedure for irreversible damage to the tissue. However, Japan, as well as many countries across the globe, are suffering from a shortage of donor supplies. Recent developments in bioengineering techniques have opened the way for the possible development of regenerated tissue from cultured progenitor cells. An artificial cornea with all the necessary cell components may become available in the near future.

Amnion↗
PubMed2002

Laser-assisted in situ keratomileusis for patients with dry eye.

OBJECTIVE: To evaluate the efficacy and safety of laser-assisted in situ keratomileusis (LASIK) in patients with preoperative dry eye. METHODS: We divided the 543 eyes that underwent LASIK into the following 3 groups: eyes with definite dry eye (DE group), with probable dry eye (PDE group), and without dry eye (NDE group). We evaluated visual outcome, dry-eye status, and complications. OUTCOME MEASURES: We compared uncorrected and best-corrected visual acuity, manifest refraction, symptoms, tear function, ocular surface abnormality, complications, corneal sensitivity, endothelial cell count, and patient satisfaction among the groups. RESULTS: We found no significant differences among the groups in uncorrected and best-corrected visual acuity, manifest refraction, and patient satisfaction. A dry-eye symptom, dryness, was more severe in the DE than the NDE group after LASIK. The mean results of the Schirmer test with anesthesia and tear breakup times were significantly lower and the fluorescein score was higher in the DE than the NDE groups after LASIK. We found no differences in the incidence of complications among the groups. Corneal sensitivity was recovered within 6 months after LASIK in the DE and PDE groups and within 3 months in the NDE group. CONCLUSIONS: The efficacy and safety of LASIK were not affected by preexisting dry eye. However, preexisting dry eye is a risk factor for severe postoperative dry eye with lower tear function, more vital staining of the ocular surface, and more severe symptoms.

Adult↗
PubMed2002

Understanding dry eye syndrome.

It was my great pleasure to have had the opportunity to give the conference address in addition to being honored by the Professor Dohlman Award. I am proud of the progress in the understanding of dry eye that has been made over the past couple of decades. However, the clinical application of the knowledge that has accumulated lies in the future. Thus far no effective medication has ever been developed for the treatment of severe dry eye. Cyclosoporine may become the first eyedrops to be used, and a series of new drugs containing androgens, immunomodulators, secretagogues, P2Y2 receptor agonists, and others may follow. I believe that medication for the treatment of dry eye will be developed in the not to distant future, and I hope that at the 4th conference in a few years time, we will be able to share these new treatments for the management of dry eye patients.

Dry Eye Syndromes↗
PubMed2002

Clinical application of living-related conjunctival-limbal allograft.

PURPOSE: To report one successful case of conjunctival-limbal allograft for the treatment of a severe ocular surface disorder. METHODS: Interventional case report. A 9-year-old patient suffering from Stevens-Johnson syndrome with total keratinization of the ocular surface of both eyes was treated in the left eye by corneal and conjunctival stem cell transplantation. Oral cyclosporin A and topical autologous serum and corticosteroids were administered. RESULTS: Mucosal epithelial phenotype was maintained in the left eye at most recent examination for more than 3 years after ocular surface reconstruction. CONCLUSION: A total keratinized ocular surface may be treated with the combination of conjunctival and corneal stem cell transplantation.

Child↗