Yukitaka Uji

Detection of early diabetic change with optical coherence tomography in type 2 diabetes mellitus patients without retinopathy.

Purpose: To detect early diabetic damage in type 2 diabetes mellitus patients with no diabetic retinopathy (NDR) using optical coherence tomography (OCT) and to evaluate OCT as a clinical test. Methods: Thirty-two patients with NDR (n = 32) were enrolled. We examined retinal and retinal nerve fiber layer (RNFL) thickness using OCT. Two healthy normal populations were also enrolled for the retinal thickness (n = 48) and RNFL thickness (n = 34). Both OCT measurements were obtained in four areas (temporal, superior, nasal and inferior). The receiver operator characteristic (ROC) curve was generated to evaluate the predictor variables. Results: Comparing the normal and NDR eyes, retinal thickness significantly increased (p = 0.03) and RNFL thickness significantly decreased (p = 0.02) in the superior areas. The area under the ROC curve was 0.65 for the superior retinal thickness and 0.63 for the superior RNFL thickness. Conclusions: Both OCT measurements can detect early retinal damage in NDR patients.

Ultrasound Biomicroscopy Dark Room Provocative Testing: ☆ ☆☆: A Quantitative Method for Estimating Anterior Chamber Angle Width

PURPOSE To describe a quantitative method for measuring the iridocorneal angle recess area, and, using this, to evaluate factors associated with appositional angle-closure during dark room provocative testing using ultrasound biomicroscopy (UBM). METHODS All patients (178 patients, 178 eyes) with clinically narrow angles referred for UBM dark room provocative testing between September 1996 and March 1998 were enrolled in this study. Images of the inferior quadrant of the angle taken under standardized dark and light conditions were analyzed. The angle recess area (ARA) was defined as the triangular area demarcated by the anterior iris surface, corneal endothelium, and a line perpendicular to the corneal endothelium drawn from a point 750 microm anterior to the scleral spur to the iris surface. ARA, and acceleration and gamma-intercept of the linear regression analysis of the ARA were calculated. In the linear regression formula, y = ax + b, the acceleration a describes the rate at which the angle widens from the scleral spur; the y-intercept b describes the distance from the scleral spur to the iris. RESULTS Under dark conditions, the angles in 99 patients (55.6%) showed evidence of appositional angle-closure during testing. ARA (0.11 +/- 0.04 vs. 0.15 +/- 0.05 mm2, P < .0001, Student t-test), acceleration a (0.22 +/- 0.15 vs. 0.26 +/- 0.17, P = .068), and y-intercept b (66 +/- 46 vs. 92 +/- 47 microm, P = .0003) were smaller in eyes that were occluded. In the eyes that were not occluded, y-intercept b showed no significant difference between light and dark conditions (P = .1, paired t-test), while acceleration a did (P < .0001). In the eyes that were occluded, both decreased significantly under dark conditions (P < .0001). CONCLUSIONS The ARA linear regression formula provides useful quantitative information about angle recess anatomy. The more posterior the iris insertion on the ciliary face, the less likely the provocative test will be positive.

Macular buckling for retinal detachment due to macular hole in highly myopic eyes with posterior staphyloma.

Purpose: To evaluate the efficacy of macular buckling surgery using a special exoplant. Methods: The authors reviewed 33 cases of patients with retinal detachment due to macular hole with posterior staphyloma who underwent a macular bucking procedure and 11 cases of patients with the same condition due to macular hole without posterior staphyloma or due to a hole along the edge of the posterior staphyloma who underwent gas injection or vitrectomy. The reattachment rate, visual acuity (VA). and area size (V‐4,1‐4 isopter) by Goldmann perimetry were calculated. Results: Reattachment rate for the macular buckling procedure was 94% (initial) and 100% (final), and that for the gas injection or vitrectomy was 100% (both initial and final). Twenty of the 33 eyes (60.6%) had VA of 20/400 or better, and none of these 33 eyes had a VA at the level of finger counting or poorer following macular buckling. Nine of the 11 eyes (81.8%) had VA of 20/400 or better, and none of these 11 eyes had a VA at the level of finger counting or poorer following the gas injection or vitrectomy. The area size of V‐4 isopter in the macular buckling group was significantly larger than that in the gas injection or vitrectomy group (P = 0.017). Conclusion: The macular buckling procedure is effective when considered both from an anatomic and a functional perspective for retinal detachment due to macular hole with posterior staphyloma.

The multifocal electroretinogram in retinal detachment.

We evaluated the retinal electrophysiologic function in both the detached and attached areas of eyes with retinal detachment, and assessed the functional recovery of these areas after surgery by quantifying the results, obtained from multifocal electroretinograms. Multifocal electroretinographic recordings and central 0°, to 30°, visual field tests were performed preoperatively and 2 weeks 1, 3 and 6 months postoperatively in 12 patients with unilateral retinal detachment. Each patients response to the multifocal electroretinogram and the visual field test was classified into two groups: group A, the response from the attached area; and group B, that from the detached retinal area. Individual mean deviation and percentage mean deviation were calculated for each group. All retinal detachments were successfully reattached by the conventional scleral buckling method. The retinal sensitivity in the visual field test of all the patients in group B greatly improved. However, the percentage mean deviation in the response density of the multifocal electroretinogram in group B was −81% preoperatively and −63% at 6 months postoperatively. Thus, the improvement was confined within narrow limits. The response density of the multifocal electroretinogram in group A was very low, and never improved beyond −50% of percentage mean deviation. In the eyes with retinal detachment, electroretinogram response in both the attached and detached areas was more disturbed, than predicted by means of the visual field test during the course of this study.

The keratin-binding protein Albatross regulates polarization of epithelial cells

The keratin intermediate filament network is abundant in epithelial cells, but its function in the establishment and maintenance of cell polarity is unclear. Here, we show that Albatross complexes with Par3 to regulate formation of the apical junctional complex (AJC) and maintain lateral membrane identity. In nonpolarized epithelial cells, Albatross localizes with keratin filaments, whereas in polarized epithelial cells, Albatross is primarily localized in the vicinity of the AJC. Knockdown of Albatross in polarized cells causes a disappearance of key components of the AJC at cell–cell borders and keratin filament reorganization. Lateral proteins E-cadherin and desmoglein 2 were mislocalized even on the apical side. Although Albatross promotes localization of Par3 to the AJC, Par3 and ezrin are still retained at the apical surface in Albatross knockdown cells, which retain intact microvilli. Analysis of keratin-deficient epithelial cells revealed that keratins are required to stabilize the Albatross protein, thus promoting the formation of AJC. We propose that keratins and the keratin-binding protein Albatross are important for epithelial cell polarization.

The Effect of the H-1152P, a Potent Rho-Associated Coiled Coil-Formed Protein Kinase Inhibitor, in Rabbit Normal and Ocular Hypertensive Eyes

Purpose: We wanted to determine the intraocular pressure (IOP)-lowering effect of H-1152P by utilizing a rabbit ocular hypertension-glaucoma model and normal eyes. H-1152P is a potent, Rho-associated, coiled, coil-forming protein kinase (ROCK) inhibitor. Methods: IOPs were monitored by a pneumatonometer in New Zealand White rabbits that were given topically administered H-1152P or vehicle alone. Animals were divided into four groups followed by topical administration of 0.1, 1.0, 10, and 28 mM H-1152P. To study the IOP-lowering effects on an elevated IOP model, a rabbit ocular hypertension model was created by water loading. All studies were carried out by monitoring of IOPs on H-1152P-administered right eyes and phosphate-buffered saline (PBS)-administered left eyes. Results: In normotensive IOP rabbits, topical administration of H-1152P significantly decreased IOPs by 46.1 ± 5.0% at 1% (28 mM) solution. This effect was dose dependent, as the maximum reduction of IOPs were observed between 60 and 90 min after topical administration (3.6 ± 0.9 mmHg, 5.4 ± 0.7 mmHg, 6.8 ± 0.7 mmHg, and 7.2 ± 1.9 mmHg at 0.1, 1.0, 10, and 28 mM H-1152P). In addition, in the rabbit ocular hypertension model, the topical administration of H-1152P (28 mM) significantly lowered IOPs starting at 30 minutes and lasting up to 300 minutes after water loading. The maximum IOP reduction, however, was observed at 90 minutes after water loading (10.6 ± 2.3 mmHg). No serious side effects were observedin ocular tissues except for some conjunctival congestion that shortly disappeared within 3 hours.Conclusion: Topical administration of H-1152P potently decreased rabbit normotensive IOPs in a dose-dependent manner, and the duration of the IOP lowering was also elongated in a dose-dependent manner. In addition, H-1152P has a potent IOP-lowering effect on an ocular hypertension model. These result suggested that H-1152P could be a candidate for the next generation of glaucoma therapy.

The Effect of the Rho-Associated Protein Kinase Inhibitor, HA-1077, in the Rabbit Ocular Hypertension Model Induced by Water Loading

Purpose: The aim of this study was to investigate the intraocular pressure (IOP)-lowering effect of a new anti-glaucoma drug, the Rho-associated protein kinase (ROCK) inhibitor, HA-1077, in a rabbit ocular hypertension model. Methods: Experiments were carried out in 18 male New Zealand white rabbits, with ocular hypertension induced by water loading. Animals were divided into three groups followed by topical administration of 1 mM, 2 mM, and 3 mM HA-1077 in the left eye. As a control, phosphate buffered saline was administered in the opposite eye. Results: After administration of HA-1077 eye drops, there was a significant time- and dose-dependent decrease of the IOP. While minor conjunctival injection was seen in a few cases, no abnormalities of the anterior chamber or fundus were observed. Conclusions: This is the first report of the effect of the ROCK inhibitor, HA-1077, on the IOP in an ocular hypertension model. Study results indicated that HA-1077 has a strong IOP-lowering effect.

Quantitative analysis of eyelash lengthening following topical latanoprost therapy.

BACKGROUND There have been several reports, mostly qualitative, of ocular side effects of latanoprost, including lengthening of eyelashes. We investigated changes in eyelash length in patients receiving topically administered latanoprost. METHODS Seventeen patients (11 men and 6 women aged 63 to 80 years) with glaucoma or ocular hypertension were treated with latanoprost (one drop to one eye daily at bedtime). All had dark brown irises. At the start of treatment and after 2, 6 and 10 weeks of treatment, a single eyelash was removed from the centre of the upper eyelid of the treated and fellow (control) eyes and measured. Adverse events (defined as any undesirable event occurring in a subject, regardless of whether it was considered related to the latanoprost treatment) were monitored carefully. At each examination patients were asked whether they had any ocular or systemic symptoms. RESULTS For the eyes treated with latanoprost, the mean eyelash length (and standard deviation) was 5.8 mm (0.7 mm) at baseline, 6.5 mm (0.6 mm) at 2 weeks, 6.5 mm (0.9 mm) at 6 weeks and 6.6 mm (0.7 mm) at 10 weeks (p < 0.001 for all differences from baseline). The corresponding values for the untreated eyes were 5.7 mm (0.7 mm), 5.8 mm (0.7 mm), 5.9 mm (0.7 mm) and 5.6 mm (0.7 mm); all differences were nonsignificant. INTERPRETATION Latanoprost significantly increases eyelash length.

Evaluation and comparison of indentation ultrasound biomicroscopy gonioscopy in relative pupillary block, peripheral anterior synechia, and plateau iris configuration

Purpose:To evaluate and compare the findings and changes of the anterior chamber angle configuration with indentation ultrasound biomicroscopy (UBM) gonioscopy in relative pupillary block (RPB), peripheral anterior synechia (PAS), and plateau iris configuration (PIC). Methods:This study included 73 eyes of 52 patients with RPB (n = 26), PAS (n = 21), or PIC (n = 26). First, a conventional UBM scan was performed using a normal size standard eye cup before indentation. Then, for indentation UBM gonioscopy, scans were performed using a new eye cup that we designed. For evaluation of the angle, angle opening distance 500 and angle recess area were recorded and evaluated with regard to the effect of expansion on the anterior chamber angle. Results:Indentation UBM gonioscopy showed the characteristic images in each of the eyes. The angle of all examined eyes was significantly widened with indentation (P < 0.01). The angle changes in eyes with RPB were significantly greater than in eyes with PAS or PIC (P < 0.01). Conclusion:Indentation UBM gonioscopy is a very useful method for observing the angle and diagnosis of RPB, PAS, and PIC.

Contribution of nitric oxide-producing cells in normal and diabetic rat retina.

PurposeTo examine the immunohistochemical localization of l-arginine and l-citrulline and determine where and how nitric oxide (NO) is produced in the normal and streptozotocin (STZ)-induced diabetic rat retinas.MethodsNO is produced when l-arginine is changed to l-citrulline by NO synthase (NOS). In normal and STZ-induced diabetic rats, using an immunohistochemical method, we examined the retinal distribution of l-arginine and l-citrulline after intracardiac perfusion. We studied the distribution of NOS after immersed fixation and analyzed the number of neuronal NOS (nNOS)-positive neurons.ResultsWe observed l-arginine localization in the internal limiting membrane (ILM), the ganglion cell layer (GCL), and the inner nuclear layer (INL). l-Arginine immunoreactivity in the diabetic rat retinas was found in the inner plexiform layer (IPL), as well as in the normal retina. l-Citrulline immunoreactivity in the normal and diabetic retinas was observed in the ILM, the GCL, the IPL, and the INL. nNOS staining in the normal and diabetic rat retinas was observed in the GCL, the IPL and the INL. The number of nNOS-positive amacrine cells was less in the diabetic rat retinas.ConclusionNO might be produced in the GCL and amacrine cells, which show immunoreactivity to l-arginine, l-citrulline, and nNOS. In the early stage of diabetic retinopathy in STZ rat retinas, diabetes disturbed the function of the nNOS-positive amacrine cells and reduced NO production via nNOS. Jpn J Ophthalmol 2005;49:363–370