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Biomedical subjects

Kazuo Tsubota

Publications and source records attributed to Kazuo Tsubota.

At least 127 records · Page 7Linked to original sources

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↗

Severe late-onset recurrent epithelial erosion with diffuse lamellar keratitis after laser in situ keratomileusis.

A 39-year-old woman had laser in situ keratomileusis that was complicated by intraoperative epithelial erosion in both eyes. Seven months after surgery, the patient returned, complaining of pain and blurred vision in the left eye. Slitlamp examination revealed corneal epithelial erosion with severe diffuse lamellar keratitis (DLK). Reepithelialization was complete in several days. However, severe inflammation remained until systemic steroids were administered. Recurrent erosions can lead to a serious inflammatory reaction such as DLK because of the presence of the flap-stroma interface.

Adult↗

Detection of neutrophils and possible involvement of interleukin-8 in diffuse lamellar keratitis after laser in situ keratomileusis.

PURPOSE: To investigate the cell populations in diffuse lamellar keratitis (DLK) infiltration after laser in situ keratomileusis and the possible mechanism underlying the infiltration. SETTING: Department of Ophthalmology, Tokyo Dental College, Chiba, Japan. METHODS: To develop DLK in rabbit eyes, 25 microL of lipopolysaccharide (LPS) solution at a concentration of 50 microg/mL was applied to the stromal bed beneath corneal flaps. For control rabbits, phosphate-buffered saline was applied. Postoperative examination by slitlamp microscopy was performed for 3 days after surgery. Rabbit eyes were excised and examined for histopathology with hematoxylin and eosin staining. Immunohistochemical analysis for interleukin (IL)-8 was performed. RESULTS: Diffuse lamellar keratitis-like inflammation composed mainly of neutrophils was reproduced by LPS instillation in rabbit eyes. In eyes with severe inflammation, IL-8 immunoreactivity was found in the stromal keratocytes and infiltrating neutrophils. CONCLUSIONS: The major cell type in the DLK infiltration induced by LPS instillation in rabbit eyes was the neutrophil. Interleukin-8, a prototype of CXC chemokine produced by keratocytes and neutrophils, may contribute to the development of DLK.

Animals↗

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↗

Tear function and ocular surface changes with topical mitomycin (MMC) treatment for primary corneal intraepithelial neoplasia.

PURPOSE: To evaluate the tear function and ocular surface alterations in patients with primary CIN before and after treatment with topical mitomycin (MMC). PATIENTS AND METHODS: We describe seven patients with unilateral CIN treated with 0.04% topical MMC three times daily until full eradication of the lesion. The patients underwent tear and ocular surface examinations including Cochet-Bonnet corneal sensitivity measurements, tear film break-up time (BUT), Schirmer test, and Rose-Bengal staining before, at the time of resolution of the CIN, and at the final follow-up. Conjunctival impression cytology was performed before treatment and at the last visit. RESULTS: The mean pretreatment corneal sensitivity was 30.3 +/- 7.4 mm and improved to 55 +/- 5 mm at the final visit (P < 0.05). There were no aqueous-deficient eyes. The BUT values and Rose-Bengal staining scores also showed significant improvement at the last follow-up compared with the pretreatment values (P < 0.05). Initial impression cytology specimens showed goblet cell loss, higher grades of squamous metaplasia, areas of isolated keratinized, binucleated, and actively mitotic disfigured epithelial cells in all patients. The mean goblet cell density and squamous metaplasia grade were observed to improve significantly at the last visit (P < 0.05). MMC-induced cytologic changes were seen to persist long after cessation of treatment in some patients. All eyes remained free of recurrence and complications during the follow-up period. CONCLUSION: We found 0.04% topical MMC treatment tid until full eradication to be effective in the management of CIN. The ocular surface disease of CIN was characterized by disturbance of tear film stability, goblet cell loss, and increased squamous metaplasia in all patients. Impression cytology proved useful in attaining the diagnosis of CIN, evaluating the effect of treatment, and showing MMC-related long-term changes on the ocular surface.

Administration, Topical↗

Collagen-poly(N-isopropylacrylamide)-based membranes for corneal stroma scaffolds.

PURPOSE: To investigate the feasibility of using the biocompatibility of collagen-based blended biomaterials as cell-delivery systems in ocular surface reconstruction in vivo. METHODS: Collagen-based composites that were blended with synthetic acrylamide-based polymers [poly(N-isopropylacrylamide), pNIPAAm] were transplanted into corneal pockets of white rabbits, with a 3-mm epithelial window. Epithelial cells were allowed to migrate onto the polymer. Transplanted eyes were examined daily for up to 30 days, after which animals were killed for histologic examination. Immunohistochemistry was performed for vimentin, alpha-smooth muscle actin (alpha-SMA), CD4, and CD8. Gold-chloride staining was performed to observe neuronal regrowth. Human amniotic membranes (AMs) and sham-operated corneas served as controls. All animals received topical antibiotics (levofloxacin) without the use of steroids or other immunosuppressive agents. RESULTS: The pNIPAAm polymer allowed smooth epithelialization of the cornea, which was similar to the epithelialization observed in sham controls and AM-transplanted eyes. Histology revealed that epithelium overlying the polymer was bundled into several layers, without the orientation observed with AM and sham controls. The polymer gradually thinned and was gradually replaced by host tissue. Vimentin- and alpha-SMA-positive cells were found in stromal pockets up to 1 month following polymer transplantation. These cells were responsible for slight subepithelial haze near the wound edge. CD4- and CD8-positive lymphocytes were also observed in the vicinity of the polymer. Gold-chloride staining showed nerve regrowth in the wound edge after 1 month and subepithelial branches after 3 months. CONCLUSION: Collagen-pNIPAAm blended polymers may be effective as biomaterials to be used in the early stages of lamellar stromal replacement

Acrylic Resins↗

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↗

Protective effect of D-beta-hydroxybutyrate on corneal epithelia in dry eye conditions through suppression of apoptosis.

PURPOSE: To investigate the effect of D-beta-hydroxybutyrate (HBA) on ocular surface epithelial disorders induced by tear fluid deficiency, the potency of HBA and serum, the efficacy of which has been well documented in clinical application, were compared. METHODS: Rat corneal epithelial erosion was induced by exposure of rat eyes to continuous low-humidity airflow, which accelerated the tear evaporation. During desiccation, one eye of each rat was treated with HBA (20, 40, or 80 mM) or rat serum (5%, 20%, or 100%), and in the other eye a drop of phosphate-buffered saline (PBS) was instilled as the control. Histopathologic examination and quantification of the epithelial defect area were performed. The apoptosis in the epithelia was determined by chromatin condensation using the Hoechst 33342 fluorescein probe. RESULTS: In PBS-treated eyes, thinning in the cell layer was seen on the periphery of the initial wound after 6 hours, and it progressed to defects after 12 hours. In the 80-mM HBA and 20% serum applications, the pathologic change in the epithelia was moderate, and the structure was maintained in an almost normal state in the 100% serum application. Significant decreases in the defect areas were observed in the 5%, 20%, and 100% serum and 40- and 80-mM HBA treatment groups compared with the PBS-treated eyes (n=12). A significant suppression of chromatin condensation was observed with HBA and serum treatment. CONCLUSIONS: These results suggest the potential clinical application of HBA for ocular surface epithelial disorders to maintain epithelial cell viability in patients with dry eye.

3-Hydroxybutyric Acid↗

Computer-synthesis of an interference color chart of human tear lipid layer, by a colorimetric approach.

PURPOSE: To synthesize an interference color chart for the specific tear lipid layer interference camera, DR-1, for the conversion of the tear film lipid layer thickness into color graphic information--that is, for the quantification of the tear interference image--by a colorimetric approach. METHODS: Because the color of the tear lipid layer interference image is visualized by a white light source interference phenomena, to produce gamma-corrected red, green, and blue (RGB) values of a specific interference color at a certain tear lipid film thickness, XYZ tristimulus values of the Commission Internationale de l'Eclairage (CIE) were obtained. XYZ tristimulus values were calculated from the light source spectrum of the DR-1 camera, the color-matching function of CIE, and the reflectance of the tear interference image in wavelengths ranging from 380 to 780 nm. These calculated interference colors were synthesized ranging from 0 nm to 1000 nm of lipid film thickness to produce a color chart. The applicability of the new color chart in the analysis of the lipid layer thickness was tested on a healthy control subject with normal tear function and a patient with dry eye who had aqueous tear deficiency and meibomian gland obstruction. RESULTS: The specific tear interference color chart for the DR-1 camera was obtained with RGB and XYZ tristimulus values. The interference chart ranged from 0 to approximately the 5th interference order. The interference colors from clinical DR-1 images could be converted to lipid thickness data by using the color chart system. CONCLUSIONS: A new tear interference color chart was developed in this study, which may be of benefit in converting tear interference color information to data describing the thickness of the tear film lipid layer.

Adult↗

[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↗

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↗

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↗

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↗

Impaired functional visual acuity of dry eye patients.

PURPOSE: To report dry eye patients' functional visual acuity, which was measured after sustained eye opening for 10-20 seconds, as a simulation of visual function of daily acts of gazing, which is defined as looking at an object with involuntary blink suppression. METHODS: Interventional clinical nonrandomized comparative trial. We measured ordinary best-corrected visual acuity and functional visual acuity in non-Sjögren's syndrome (non-SS, N = 10) and Sjögren's syndrome (SS, N = 12) patients and in normal controls (N = 8), prospectively. Surface regularity index (SRI) of corneal topography was also measured under routine circumstances and after sustained eye opening. Blink rates while gazing were measured during reading in another 28 dry eye patients and during driving in another 8 normal controls. RESULTS: Functional visual acuity did not change (1.27-1.16) in normal controls, but decreased significantly from 1.18-0.336 in non-SS patients (P = .0007) and from 1.15-0.228 (P < .00001) in SS patients. SRI after sustained eye opening increased in non-SS (P = .032) and SS patients (P = .0007), but not in the normal controls. Blink rates during reading (P < .001) and driving (P = .012) were significantly decreased from baseline blink rates. CONCLUSIONS: This study shows that the visual function of dry eye patients becomes abnormal with ocular surface irregularity when the eye is kept open for 10-20 seconds. Our data indicate impaired visual function in dry eye patients while gazing. Functional visual acuity may be important in daily activities.

Automobile Driving↗

Visual protective sheet can increase blink rate while playing a hand-held video game.

PURPOSE: To evaluate the effectiveness of a protective sheet in reducing eye strain caused by unnecessary light reflection on portable liquid crystal display panels while playing Game Boy (Nintendo, Kyoto, Japan). DESIGN: Nonrandomized clinical trial. METHODS: The blink rates of 24 normal volunteers were measured under relaxed conditions while viewing a portable liquid crystal display panel and playing Game Boy with and without the protective sheet of polyethylene terephthalate with antiglare coating for a total of 10 minutes each. RESULTS: The results showed a dramatic increase (from 5.6 +/- 3 to 9.1 +/- 4.9 [P <.0001]) in blinks/minute with use of the protective sheet. CONCLUSION: The protective sheet has shown the possibility of increasing the blink rate by making the screen easier to see.

Adult↗