Biomedical subjects

Kazuo Tsubota

Publications and source records attributed to Kazuo Tsubota.

At least 91 records · Page 5Linked to original sources

PubMed2005

Serum-free spheroid culture of mouse corneal keratocytes.

PURPOSE: To develop a serum-free mass culture system for mouse keratocytes. METHODS: Corneas of C57BL6/J mice were enzyme digested after the epithelium and endothelium were removed. Stromal cells were cultured in serum-free DMEM/F12 (1:1) containing epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2), and B27 supplement. Primary spheres were dissociated by trypsin and subcultured as suspended secondary spheres. Cells from postnatal day (P)6 to P10 spheres were subcultured onto plastic dishes or type I collagen gels for phenotype analysis. The expression of the keratocyte markers keratocan, aldehyde dehydrogenase (Aldh), and CD34, were analyzed by RT-PCR, and vimentin and alpha-smooth muscle actin (alpha-SMA) were examined by immunocytochemistry. RESULTS: Primary keratocytes formed spheres, which were cultured for over 12 passages. Suspended sphere cells expressed vimentin, keratocan, CD34, and lumican, but were negative for cytokeratin K12 (K12) and Pax6. Sphere cells subcultured on plastic exhibited a dendritic morphology characteristic of keratocytes, and maintained keratocan, Aldh, and CD34 expression in serum-free medium. Sphere cells subcultured with 10% serum became fibroblastic, and expressed alpha-SMA when stimulated by transforming growth factor (TGF)-beta. alpha-SMA-positive cells demonstrated contractile properties on collagen gels, compatible with the myofibroblast phenotype. CONCLUSIONS: The phenotype of mouse keratocytes can be maintained in vitro for more than 12 passages by the serum-free sphere culturing technique.

Animals↗

PubMed2005

Suppression of ocular inflammation in endotoxin-induced uveitis by blocking the angiotensin II type 1 receptor.

PURPOSE: To examine whether the angiotensin II type 1 receptor (AT1-R) signaling plays a role in ocular inflammation in endotoxin-induced uveitis (EIU). METHODS: EIU was induced in C57BL/6 mice by a single intraperitoneal injection of 150 mug lipopolysaccharide (LPS). Tissue localization, mRNA expression, and protein levels of AT1-R in murine retinas were examined by immunohistochemistry, RT-PCR, and Western blot analyses, respectively. Telmisartan, an AT1-R antagonist widely used as an antihypertensive agent, was administered intraperitoneally at a dose of 10 mg/kg daily for 5 days until the injection of LPS. Twenty-four hours after administration, leukocyte adhesion to the retinal vasculature was evaluated with a concanavalin A lectin perfusion-labeling technique. Retinal mRNA and protein levels of intercellular adhesion molecule (ICAM)-1 were examined by RT-PCR and ELISA, respectively. Protein concentration and inflammatory cells in the aqueous humor were also measured. RESULTS: Retinal vessels were positive for AT1-R. In mice with EIU, retinal AT1-R mRNA and protein levels were significantly increased when compared to the normal control. EIU animals also showed significant increases in the number of inflammatory cells infiltrating the anterior chamber and adhering to the retinal vessels and in retinal ICAM-1 levels. Administration of telmisartan to EIU mice resulted in significant suppression of retinal ICAM-1 expression and leukocyte adhesion and infiltration compared with vehicle treatment. Protein concentration in the aqueous humor of telmisartan-treated EIU mice tended to be lower than that of vehicle-treated EIU mice, but the difference was not statistically significant. CONCLUSIONS: AT1-R signaling blockade inhibited retinal ICAM-1 upregulation and leukocyte adhesion and infiltration in the EIU model. These results suggest the potential use of an AT1-R antagonist as a therapeutic agent to reduce ocular inflammation.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal fibroblasts on the pathogenesis of allergic keratopathy.

OBJECTIVE: The present study investigated the expression of ICAM-1 and VCAM-1 on fibroblasts with interleukin (IL)-4 and/or tumor necrosis factor (TNF)-alpha stimulation and assessed the effect of eosinophil adhesion on fibroblast viability. METHODS: Primary cultured human corneal fibroblasts were incubated with IL-4, TNF-alpha, or their combination for 24 hours. Expression of ICAM-1 and VCAM-1 was examined by real-time quantitative PCR and flow cytometric analysis. Purified eosinophils were cocultured with activated fibroblasts, and the number of eosinophils adhered to fibroblasts and the number of damaged fibroblasts were counted using microscopy. In a separate trial, conjunctival and corneal impression cytology was performed on patients with atopic keratoconjunctivitis and corneal ulcers (eight eyes) to assess the status of the ocular surface epithelium and the presence of inflammatory cell infiltrates. RESULTS: Real-time quantitative PCR and flow cytometric analysis revealed that both mRNA and protein of VCAM-1 and ICAM-1 were upregulated by IL-4 and TNF-alpha. IL-5-primed eosinophils adhered to the corneal fibroblasts treated with IL-4 and TNF-alpha, and the fibroblasts were damaged by eosinophil adherence. Anti-ICAM-1 antibody and anti-VCAM-1 antibody inhibited the eosinophil adherence to fibroblasts and the fibroblast damage. Impression cytology revealed extensive infiltration of neutrophil and eosinophils among isolated ocular surface epithelial cells with advanced squamous metaplasia. CONCLUSIONS: Corneal fibroblasts expressed ICAM-1 and VCAM-1 when activated with IL-4 and TNF-alpha. Eosinophils can adhere to the activated fibroblasts and can induce subsequent fibroblast damage through these adhesion molecules. Eosinophil adhesion to fibroblasts may possibly contribute to the pathogenesis of severe persistent allergic corneal ulcers.

Cell Adhesion↗

PubMed2005

Hypoxia induces the expression of membrane-type 1 matrix metalloproteinase in retinal glial cells.

PURPOSE: Fibrovascular tissue formation in diabetic retinopathy necessitates not only angiogenic activity but also proteolytic activity, which is at least in part attributable to the induction of membrane-type 1 matrix metalloproteinase (MT1-MMP) in retinal glial cells. However, little is known about the triggers for MT1-MMP induction in the diabetic retina. In the present study, the effect of tissue hypoxia on MT1-MMP expression in retinal glial cells was investigated. METHODS: Retinal glial cells were isolated from the rabbit retina and cultured under either normoxic (20% O(2)) or hypoxic (1% O(2)) conditions in the presence or absence of the inhibitor for vascular endothelial growth factor (VEGF) receptor signal transduction or a neutralizing antibody against VEGF. The expression level of MT1-MMP in retinal glial cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, Western blot analysis and immunocytochemistry. Expression of VEGF and VEGF receptors, VEGFR-1 and VEGFR-2, was also examined by RT-PCR. RESULTS: RT-PCR and real-time PCR analyses showed a 2.3-fold induction of MT1-MMP expression in retinal glial cells under hypoxic conditions. VEGF, especially its isoform VEGF(165), and VEGFR-2 were also upregulated in retinal glial cells by hypoxia, and hypoxia-induced MT1-MMP expression was inhibited in the presence of the VEGFR-2 inhibitor SU1498 or the anti-VEGF antibody. CONCLUSIONS: Hypoxia can induce MT1-MMP expression in retinal glial cells, and the hypoxia-induced expression of MT1-MMP is mediated by VEGF in an autocrine fashion.

Animals↗

PubMed2005

Tryptase increases proliferative activity of human conjunctival fibroblasts through protease-activated receptor-2.

PURPOSE: Tryptase that is released by mast cell degranulation has recently been thought to play a key role in wound healing in allergic bronchitis. Conjunctival fibroblasts secrete mediators and extracellular matrices that could exacerbate inflammation and papillary formation in allergic conjunctivitis. This study was conducted to investigate the effect of tryptase on the proliferation of conjunctival fibroblasts and studied whether this effect was mediated by protease-activated receptor (PAR)-2. METHODS: Conjunctival fibroblasts were cultured with or without tryptase (0.1 ng/mL to 1.0 microg/mL), and the proliferation rate was assessed after 48 hours. The effects of tryptase inhibitors (leupeptin, benzamidine) and a PAR-2 agonist (SLIGKV) were examined. The existence of PAR-2 mRNA and protein in conjunctival fibroblasts was examined by RT-PCR and Western blot analysis, respectively. The existence of PAR-2 in cultured conjunctival fibroblasts and conjunctival papillae from patients with vernal keratoconjunctivitis, as well as conjunctival tissue from normal subjects was examined by immunohistochemistry. RESULTS: Conjunctival fibroblast proliferation was upregulated by tryptase in a dose-dependent manner (P < 0.001). Leupeptin and benzamidine inhibited tryptase-induced fibroblast proliferation (P < 0.05), and SLIGKV mimicked tryptase's effect. PAR-2 mRNA and protein were detected in cultured conjunctival fibroblasts using RT-PCR and Western blot analysis. PAR-2 immunoreactivity in both the cultured conjunctival fibroblasts and in stromal cells in excised conjunctival tissues was observed. CONCLUSIONS: Tryptase increased conjunctival fibroblast proliferation and this response appeared to be mediated by PAR-2. Mast cells are the most likely source of tryptase in the conjunctiva and may play an important role in chronic exacerbations with conjunctival papillary formation in allergic conjunctivitis.

Benzamidines↗

PubMed2004

Efficacy and safety of international donor sharing: a single-center, case-controlled study on corneal transplantation.

BACKGROUND: To overcome the shortage of donor corneas, we are currently using donor corneas supplied by foreign eye banks. This single-center, case-controlled study was conducted to show the efficacy and safety of corneal transplantation using corneas from foreign donors. METHODS: A retrospective, case-controlled comparison of 118 corneal transplants using foreign donor corneas (foreign group) and domestic donor corneas (domestic group) was performed. The two groups were matched according to original disease, age, severity of preoperative neovascularization, and history of previous grafting. Clinical outcome and incidence of postoperative complications were compared between the two groups. RESULTS: The foreign group had a longer preservation-to-operation time than the domestic group, reflecting the longer transportation time. However, the incidence of clear grafts and postoperative complications such as immunologic rejection, infection, and glaucoma was not significantly different between the two groups. CONCLUSIONS: Corneal transplantations using foreign donor corneas are as effective and safe as those using domestic donor corneas, despite the longer preservation time.

Case-Control Studies↗

PubMed2004

Therapeutic effect of cevimeline on dry eye in patients with Sjögren's syndrome: a randomized, double-blind clinical study.

PURPOSE: Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by salivary and lacrimal glandular destruction leading to symptoms of dry mouth and dry eye. Dryness can also occur in the absence of glandular destruction. Patients with SS have autoantibodies that bind to muscarinic acetylcholine receptors in the exocrine glands. Recently, a muscarinic acetylcholine receptor agonist, cevimeline, has been approved for use against symptoms of dry mouth in patients with SS. In this study, the efficacy of cevimeline in improving symptoms of dry eye was examined. DESIGN: Prospective, randomized, double-blind, multi-center clinical study. METHODS: Sixty patients were randomly assigned to three groups-placebo; cevimeline, 20 mg three times daily; or cevimeline, 30 mg three times daily-and received treatment for 4 weeks. Patients were evaluated before treatment, at week 2, at the end of treatment, and at the end of a 2- to 4-week follow-up period. RESULTS: Compared with the placebo, statistically significant differences were seen with cevimeline, 20 mg three times daily, in subjective symptoms, tear dynamics, condition of the corneoconjunctival epithelium, and global improvement rating. No difference was found among the three groups regarding the safe use of the drug. CONCLUSIONS: These results indicate that cevimeline, 20 mg three times daily, is safe and effective in improving symptoms of dry eye in patients with SS. Additional studies, with larger patient populations, are needed to further assess the effectiveness of cevimeline for dry eye.

Conjunctiva↗

PubMed2004

Ocular surface changes with applanation contact lens and coupling fluid use after argon laser photocoagulation in noninsulin-dependent diabetes mellitus.

PURPOSE: To describe the effect of coupling solutions used during laser photocoagulation on the ocular surface of patients with noninsulin-dependent diabetes mellitus (NIDDM). DESIGN: A prospective case-controlled study. METHODS: Ninety-two eyes of 46 NIDDM patients with clinically significant macular edema, poor metabolic control of diabetes, and peripheral neuropathy and 100 eyes of 50 normal control subjects were studied. The patients' eyes were assigned to argon green focal/grid laser photocoagulation using an applanation contact lens and one of the coupling fluids; 2% methocel, Thilo-Tears Gel, 1.4% sodium hyaluronate, or 0.9% simple saline. The control subjects received time-matched three-mirror contact lens fundus examinations. All subjects underwent corneal sensitivity measurements, Schirmer test, tear film breakup time, and corneal fluorescein staining before as well as 3 and 8 days after the laser procedures and contact lens examinations. Patients with corneal problems persisting after 8 days were followed longer. RESULTS: Diabetic eyes assigned to 2% methocel and 1.4% sodium hyaluronate had significantly lower mean corneal sensitivities and break-up time values as well as significantly higher mean fluorescein staining scores at all examination points after laser photocoagulation. All diabetic eyes with aqueous deficiency assigned to 2% methocel and 1.4% sodium hyaluronate developed delayed corneal epithelial healing. CONCLUSION: The use of viscous coupling solutions during applanation contact lens-aided laser procedures may be detrimental for the corneal epithelium in poorly controlled NIDDM patients with peripheral neuropathy and coexisting aqueous deficiency.

Adult↗

PubMed2004

Lidocaine tape (Penles) reduces the pain of botulinum toxin injection for Meige syndrome.

PURPOSE: To evaluate the efficacy of lidocaine tape in reducing pain during botulinum toxin injection. DESIGN: Randomized double-blind study. METHOD: Six men and four women with a diagnosis of Meige syndrome undergoing botulinum toxin injection were recruited. Lidocaine tape was applied to the eyelid skin of a randomly selected eye and placebo tape to the other eye. Pain during botulinum toxin injection was evaluated subjectively by a visual analogue scale. Side effects were also monitored. RESULTS: Mean subjective pain both on puncturing skin and on injection in the lidocaine group was significantly lower than that in the placebo group. Nine of 10 patients found lidocaine tape to be more effective than placebo tape in reducing pain during injection. CONCLUSIONS: Lidocaine tape is a simple and convenient method of reducing pain during botulinum toxin injection. This method is recommended for patients reluctant to receive this treatment because of pain during injection.

Anesthesia, Local↗

PubMed2004

Risk factors and retreatment results of intraoperative flap complications in LASIK.

PURPOSE: To evaluate the incidence, type, and risk factors of intraoperative complications leading to abandonment of laser in situ keratomileusis (LASIK), and to compare the safety and efficacy of retreated LASIK with uncomplicated primary LASIK. SETTING: Refractive surgery centers in Tokyo, Yokohama, Nagoya, Osaka, and Fukuoka, Japan. METHODS: A total of 3751 eyes of 2033 patients who were followed for 6 months after primary LASIK, of which 15 eyes were retreated after intraoperative flap complications, were reviewed. In most of the cases, retreatments were performed by recutting a new flap. RESULTS: Intraoperative flap complications occurred in 25 eyes, of which 15 eyes had retreatment at a later date. The overall incidence of complications was independent of the surgeons' experience, although incomplete flaps, in particular, occurred at a higher rate in the hands of inexperienced surgeons. No patient profile was detected as a risk factor for intraoperative flap complications. No flap-related complications occurred at retreatment. Refractive and visual outcomes were comparable to those in the uncomplicated cases within 6 months postoperatively. CONCLUSIONS: Retreatment after microkeratome flap complications by recutting the cornea is safe and effective.

Adult↗

PubMed2004

Early visual results with the rollable ThinOptX intraocular lens.

PURPOSE: To prospectively assess the clinical and visual outcomes of phacoemulsification and implantation of a rollable intraocular lens (IOL) with a thin optic and compare the results with those of implantation of a foldable acrylic IOL. SETTING: Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan. METHODS: Sixteen consecutive eyes of 8 patients (4 women, 4 men) with corticonuclear cataract had small-incision clear corneal phacoemulsification with implantation of a rollable ThinOptX IOL (ThinOptX Inc.) in the capsular bag. Twenty eyes of 10 age- and sex-matched patients (5 women, 5 men) with the same diagnosis had phacoemulsification and intracapsular implantation of an AcrySof foldable acrylic IOL (MA60BM, Alcon). The patients' refractive status and uncorrected and best corrected distance visual acuities were assessed preoperatively and 1 week and 1, 3, and 6 months after surgery. The uncorrected and best corrected near acuities were measured before and 6 months after surgery. Contrast visual acuity was measured with variable contrast charts 1, 3, and 6 months after surgery, and the results in the 2 IOL groups were compared. Anterior segment photography, intraocular pressure (IOP) measurement, specular microscopy, and fundoscopy were done before surgery and at 1, 3, and 6 months. RESULTS: The final best corrected distance acuity was better than 20/25 in all eyes with a ThinOptX IOL and 18 eyes (90%) with an AcrySof IOL. The best corrected near acuity was better than 20/40 in 12 eyes (75%) and 14 eyes (70%), respectively. The mean contrast acuity with charts 2 and 3 was significantly higher in the ThinOptX group than in the AcrySof group at all examinations (P<.05). The final mean postoperative induced astigmatism was 0.06 diopter (D) +/- 0.50 (SD) and 0.25 +/- 0.68 D, respectively (P>.05). There were no differences in IOP or corneal endothelial cell density between the 2 groups at any examination. No intraoperative or postoperative complications occurred. CONCLUSIONS: ThinOptX IOL implantation provided best corrected near and distance visual acuities comparable to those provided by the AcrySof IOLs. The significantly higher contrast acuities attained after implantation of the ThinOptX lens may be attributable to its ultrathin properties.

Acrylic Resins↗

PubMed2004

Role of the endothelial pump in flap adhesion after laser in situ keratomileusis.

PURPOSE: To investigate the role of the endothelial pump in the attachment of the corneal flap during the early period after laser in situ keratomileusis (LASIK). SETTING: Department of Ophthalmology, Tokyo Dental College, Tokyo, Japan. METHODS: The study comprised 30 porcine eyes. In all eyes, a corneal flap was made with a microkeratome. Five minutes after the flap was placed over the bed, the adhesion strength was measured with a load-testing machine. To inhibit the endothelial pump, ouabain was injected into the anterior chamber (10 eyes) or the endothelium was mechanically scraped (10 eyes). The control group included 10 eyes. RESULTS: The load needed to lift the flap was significantly lower in the ouabain group (0.21 gram force [gf]; P<.01) and the endothelial scrape group (0.22 gf; P<.01) than in the control group (0.61 gf). CONCLUSION: The endothelial pump plays an important role in flap attachment in the early postoperative period after LASIK.

Animals↗

PubMed2004

Effect of preoperative tear function on early functional visual acuity after laser in situ keratomileusis.

PURPOSE: To assess the effect of preoperative tear function on early changes in functional visual acuity (FVA) after laser in situ keratomileusis (LASIK). SETTING: Minamiaoyama Eye Clinic, Tokyo, Japan. METHODS: This prospective single-center study assessed the effect of preoperative and postoperative tear functions on FVA in 30 eyes of 15 patients who had LASIK. Functional visual acuity was defined as the binocular recognition acuity measured by the FVA tester (Wellsystem) during a 10-second, blink-free period. All patients had a Schirmer test with anesthesia and tear-film breakup time (BUT) measurements preoperatively and 1 day and 1 week after LASIK. Corneal topography and Landolt visual acuity and FVA measurements were performed before surgery and 1 day and 1 week after LASIK. Eyes with a Schirmer test reading less than 5.0 mm and a BUT less than 5 seconds were grouped as definite dry eye (DDE). Eyes with a normal Schirmer test score but a shortened BUT were grouped as probable dry eye (PDE). RESULTS: In all patients, the best uncorrected Landolt visual acuity was 20/20 or better at the postoperative examination times. In the DDE group, the mean preoperative FVA declined from 1.2 to 0.75 +/- 0.16 (SD) at 1 day and increased to 1.2 at 1 week. No change in FVA was observed postoperatively in the PDE group. CONCLUSION: Laser in situ keratomileusis patients with low basal tearing and full uncorrected distance Landolt acuity may experience a transient decrease in FVA that returns to baseline within 1 week.

Adult↗

PubMed2004

Donor source affects the outcome of ocular surface reconstruction in chemical or thermal burns of the cornea.

PURPOSE: To study the association between surgical approach and postoperative results in chemical and thermal burns of the cornea. DESIGN: Retrospective, interventional, noncomparable case series. PARTICIPANTS: Thirty-two eyes of 32 patients with chemical (n = 27) or thermal (n = 5) burns of the cornea that were associated with total limbal dysfunction. Eight eyes had a history of previous keratoplasty. INTERVENTION: Patients were treated by amniotic membrane transplantation combined with either conjunctivolimbal autograft transplantation (autograft group, n = 11) or keratolimbal allograft transplantation (allograft group, n = 21). Fifteen eyes had simultaneous penetrating keratoplasty (simultaneous group), and 6 had keratoplasty several months after ocular surface reconstruction (2-step group). MAIN OUTCOME MEASURES: Reconstruction of the corneal surface by corneal epithelium, clarity of the cornea, and incidence of postoperative complications. The outcome was compared between the autograft and allograft groups and also between the simultaneous and 2-step groups. RESULTS: At final examination, 17 eyes (53.1%) showed stable corneal epithelialization. Preoperative conditions were similar in the autograft and allograft groups and also in the simultaneous and 2-step groups. The autograft group showed significantly better results than the allograft group in both corneal epithelialization (Kaplan-Meier analysis, P = 0.003) and clear cornea (P = 0.010). Although the incidences of corneal epithelialization and clear corneas did not significantly differ between the simultaneous and 2-step groups, the former had a higher rate of endothelial rejection in the central graft (P = 0.019). CONCLUSIONS: In chemical or thermal burns of the cornea with monocular involvement, autografting should be considered as a first choice of surgery. Even in eyes with opaque corneal stroma, it may be safer to perform ocular surface reconstruction first, followed by keratoplasty as a secondary procedure.

Adolescent↗

PubMed2004

Tear function and ocular surface findings in premature and term babies.

OBJECTIVE: To describe the ocular surface and tear function findings in premature and term babies. DESIGN: Prospective, case-control study. PARTICIPANTS: Forty-eight eyes of 24 premature babies seen at the Department of Ophthalmology of Uludag University School of Medicine, Bursa, Turkey, from March 2002 through September 2002 and 50 eyes of 25 healthy term babies were studied. INTERVENTION: The subjects underwent routine ophthalmic examinations; corneal sensitivity measurements; Schirmer test with anesthesia, with and without nasal stimulation; primary Jones test; fluorescein staining of the ocular surface; and conjunctival impression cytology. MAIN OUTCOME MEASURES: Premature and term babies were compared for corneal sensitivity, lacrimal drainage system patency, tear function and ocular surface staining parameters, goblet cell density, and squamous metaplasia grade. The relation of these parameters to the status of the ocular surface was also investigated. RESULTS: Mean corneal sensitivity scores were 45+/-5.0 mm and 55+/-4.5 mm in the premature and term babies, respectively (P<0.001). Premature babies had a mean corneal fluorescein staining score of 1.5+/-0.25 points, compared with 0.22+/-0.28 points in the term babies (P<0.001). The mean Schirmer test scores without and with stimulation were 1.5+/-2.5 mm and 4.15+/-2.5 mm in the premature babies, respectively, compared with 15+/-3.5 mm and 18.75+/-4.5 mm in the term babies. The intragroup and intergroup Schirmer test scores were statistically significant (P<0.001). The primary Jones test was positive in 20.8% of the eyes in the premature babies, whereas it was positive in 84% of eyes in the term babies. The premature babies with positive primary Jones test results all had corneal epithelial defects or severe superficial punctuate keratopathy. Mean conjunctival impression cytology squamous metaplasia scores were 1.86+/-1.2 in the premature babies and 0.86+/-0.47 in the term babies (P<0.001). Mean goblet cell densities were 393+/-484 cells/mm(2) and 739+/-503 cells/mm(2) in the premature and term babies, respectively (P<0.001). CONCLUSION: Decreased corneal sensitivity, reduced tearing, and lacrimal drainage patency are important determinants of ocular surface disease in premature infants. Premature newborns with low Schirmer test scores and a patent lacrimal system may experience corneal and conjunctival epithelial problems and should be carefully checked for the presence of dry eye complications.

Case-Control Studies↗

PubMed2004

Punctal occlusion in the management of chronic Stevens-Johnson syndrome.

PURPOSE: To evaluate the effect of lacrimal punctal occlusion in the management of the ocular surface disease in chronic Stevens-Johnson syndrome. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Thirty-one eyes of 18 patients with chronic Stevens-Johnson syndrome seen at the Department of Ophthalmology of the Tokyo Dental College were studied. INTERVENTION: Patients' lacrimal puncta were occluded by cauterization or with punctal plugs. MAIN OUTCOME MEASURES: The effect of lacrimal punctal occlusion was evaluated by changes in subjective symptoms, best-corrected visual acuity (VA), Schirmer test, tear clearance test, and ocular surface double vital staining before and after punctal occlusion. RESULTS: After lacrimal punctal occlusion, symptomatic improvement was observed in 19 eyes (61.3%). The mean logarithmic VA showed significant improvement from -0.64+/-0.87 to -0.52+/-0.86 (P<0.05). The Schirmer I test results before punctal occlusion yielded a mean score of 7.4+/-8.7 mm, which changed to 10.2+/-8.3 mm after punctal occlusion. The mean preocclusion and postocclusion tear clearance values were 7.5+/-6.6 times and 4.9+/-4.8 times, respectively. The Rose Bengal staining score decreased from 4.7+/-2.8 to 2.7+/-2.2 points (P<0.05), and the fluorescein staining score decreased from 5.0+/-2.3 to 2.2+/-2.5 points (P<0.05), respectively. CONCLUSIONS: Concurrent improvements in subjective symptoms, vital staining scores, and VA point to the favorable effects of lacrimal punctal occlusion for the ocular surface health in chronic Stevens-Johnson syndrome.

Adolescent↗

PubMed2004

Autologous serum application in the treatment of neurotrophic keratopathy.

OBJECTIVE: To evaluate the effect of autologous serum application for epithelial disorders in neurotrophic keratopathy (NK). DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Fourteen eyes of 11 patients with NK seen at Tokyo Dental College, Ichikawa General Hospital, Department of Ophthalmology, were studied. INTERVENTION: Twenty percent topical autologous serum eye drops were applied 5 to 10 times daily until resolution of the NK. Patients underwent routine ophthalmic examinations, including slit-lamp examination, corneal fluorescein dye testing, Cochet-Bonnet corneal sensitivity (Luneau, France), and best-corrected visual acuity (BCVA) measurements before and at the end of the treatment. Moreover, serum samples from 10 healthy volunteers were studied for the levels of substance P (SP), insulinlike growth factor (IGF-1), and nerve growth factor (NGF) by using radioimmunoassay and enzyme-linked immunosorbent assay techniques. Tear samples from 3 healthy subjects also were analyzed for NGF and IGF-1 levels by the same techniques. MAIN OUTCOME MEASURES: The changes in corneal disease state, corneal sensitivity, and BCVA with treatment were evaluated. The levels of neural healing factors like SP, IGF-1, and NGF in serum as well as NGF and IGF-1 in tears of healthy subjects also were examined. RESULTS: The epithelial disorders healed completely in all eyes within 6 to 32 days (mean, 17.1+/-8.0 days), with a decrease in corneal scarring. The mean pretreatment corneal sensitivity was 11.8+/-11.6 mm, which increased to 30.0+/-22.9 mm after treatment at the last follow-up. Five eyes attained normal corneal sensitivity with treatment. The BCVA improved by >2 Landolt lines in 78.6% of the eyes. The mean concentrations of SP in diluted and undiluted serum were 31.4+/-8.4 pg/ml and 157.0+/-42.1 pg/ml, respectively. The mean respective concentrations of IGF-1 in diluted and undiluted serum were 31.4+/-14.8 ng/ml and 157.0+/-73.9 ng/ml. The mean concentrations for NGF were 93.6+/-63.5 pg/ml and 468.3+/-317.4 pg/ml in serum samples with and without dilution, respectively. The mean concentration of NGF in tears was found to be 54 pg/ml. Insulinlike growth factor 1 was not detected in tears in this study. CONCLUSIONS: Autologous serum harbors neurotrophic factors. Autologous serum treatment may provide neural healers to the compromised ocular surface and seems promising for the restoration of the ocular surface epithelial integrity in patients with NK.

Adult↗

PubMed2004

New insights into the diagnosis and treatment of dry eye.

Over the past decade, numerous advances have been made in relation to dry eye diagnostic markers, technologies, and treatment options. The mainstay of treatment of dry eye is the use of artificial tear solutions and punctum plugs. A goal is the development of agents that provide symptomatic treatment and, at the same time, improve ocular surface keratinization. It is the authors' opinion that the functional visual acuity tester and the new tear stability analysis system will be widely used to improve diagnosis and evaluate treatment outcomes in KCS. Advances in treatment will utilize anti-inflammatory agents, immune suppressants such as Cyclosporin A and FK-506, growth hormones, androgens, topical mucins and ocular surface stimulating drugs, like INS365. Although aqueous-deficient dry eye is most commonly not associated with Sjogren syndrome (SS), aqueous-deficient dry eye is often most severe in patients with SS; thus, this article focuses mainly on SS-associated dry eye.

Journal Article↗