Shunji Yokokura

Significant correlations between optic nerve head microcirculation and visual field defects and nerve fiber layer loss in glaucoma patients with myopic glaucomatous disk

Background Eyes with glaucoma are characterized by optic neuropathy with visual field defects in the areas corresponding to the optic disk damage. The exact cause for the glaucomatous optic neuropathy has not been determined. Myopia has been shown to be a risk factor for glaucoma. The purpose of this study was to determine whether a significant correlation existed between the microcirculation of the optic disk and the visual field defects and the retinal nerve fiber layer thickness (RNFLT) in glaucoma patients with myopic optic disks. Methods Sixty eyes of 60 patients with myopic disks were studied; 36 eyes with glaucoma (men:women = 19:17) and 24 eyes with no ocular diseases (men:women = 14:10). The mean deviation (MD) determined by the Humphrey field analyzer, and the peripapillary RNFLT determined by the Stratus-OCT were compared between the two groups. The ocular circulation was determined by laser speckle flowgraphy (LSFG), and the mean blur rate (MBR) was compared between the two groups. The correlations between the RNFLT and MBR of the corresponding areas of the optic disk and between MD and MBR of the optic disk in the glaucoma group were determined by simple regression analyses. Results The average MBR for the entire optic disk was significantly lower in the glaucoma group than that in the control group. The differences of the MBR for the tissue in the superior, inferior, and temporal quadrants of the optic disk between the two groups were significant. The MBR for the entire optic disk was significantly correlated with the MD (r = 0.58, P = 0.0002) and the average RNFLT (r = 0.53, P = 0.0008). The tissue MBR of the optic disk was significantly correlated with the RNFLT in the superior, inferior, and temporal quadrants. Conclusions Our study suggests that there is a causal relationship between the thinner RNFLT that led to the MD and reduction in the microcirculation in the optic nerve head.

A method for enhancing the ocular penetration of eye drops using nanoparticles of hydrolyzable dye.

This report describes a method for enhancing the ocular penetration of eye drops using nanoparticles of hydrolyzable dye, which is similar to a prodrug approach. The entry of eye drops into the ocular globe is restricted predominantly by corneal barrier functions. The barrier functions are epithelial tight junctions as well as a physicochemical property consisting of the opposite characteristics of a lipophilic epithelium and a hydrophilic stroma. We found that using a formulation of nanoparticles of hydrolyzable dye (with particles of 200 nm in diameter on average) attained a greater than tenfold higher (about 50-fold) ocular penetration than that of micron-sized particles. The nanoparticles were prepared by a carrier-free technique; i.e., the reprecipitation method. Confocal laser fluorescence microscopy showed that dyes originating from the nanoparticles surmounted the corneal epithelium barrier, which has tight junctions, and achieved deeper penetration into the cornea. The high penetration rate of the dyes into the cornea was attributed to the size of particles (i.e., nanoparticles) and a transformation of dye polarity from lipophilic to hydrophilic in in vivo hydrolysis reactions. We concluded that utilizing in vivo hydrolysis reactions to alter the physicochemical nature of nanoparticles consisting of hydrolyzable compounds was an effective approach for enhancing the ocular penetration of eye drops.

Association between optic nerve blood flow and objective examinations in glaucoma patients with generalized enlargement disc type.

Background The purpose of this study was to investigate the correlations between microcirculation in the optic disc, average peripapillary retinal nerve fiber layer thickness cupping parameters, and visual field defects in glaucoma patients with the generalized enlargement disc type. Methods A total of 38 eyes from 38 glaucoma patients with the generalized enlargement disc type were included. The microcirculation of the optic nerve head was examined with laser speckle flow graphy, and the mean blur rate in all areas, in vessel area, and in tissue area were calculated using the laser speckle flow graphy analyzer software. Average peripapillary retinal nerve fiber layer thickness was measured using Stratus optical coherence tomography, and cupping parameters were accessed using the Heidelberg retina tomograph. The mean deviation in the Humphrey field analyzer (30-2 SITA standard) was analyzed. The correlation between these parameters was evaluated using the Spearman rank correlation coefficient. Results The correlation coefficient of mean blur rate in all optic disc area to the average peripapillary retinal nerve fiber layer thickness, vertical C/D, and mean deviation were r = 0.7546 (P < 0.0001), r = −0.6208 (P < 0.0001), and r = 0.6010 (P = 0.0001), respectively. The mean blur rate in tissue area of the optic disc showed r = 0.7305 (P < 0.0001), r = −0.6438 (P < 0.0001), and r = 0.6338 (P < 0.0001). Conclusion We found that the mean blur rate in the optic disc was significantly correlated with the average peripapillary retinal nerve fiber layer thickness, vertical C/D, and mean deviation in patients with the generalized enlargement disc type of glaucoma. In particular, the mean blur rate in tissue area was more highly correlated than the vessel area with other results of examination in glaucoma patients with the generalized enlargement disc type.

The Influence of Posture Change on Ocular Blood Flow in Normal Subjects, Measured by Laser Speckle Flowgraphy

Abstract Purpose: To investigate, using laser speckle flowgraphy (LSFG), the autoregulation of ocular blood flow (BF) in response to posture change. Methods: This study comprised 20 healthy volunteers (mean age 30.0 ± 8.5). The mean blur rate (MBR) of the ocular circulation in the subjects was assessed in both a sitting and a supine position every 2 min over the course of 10 min. Baseline measurements of the MBR at the optic nerve head (ONH) and the choroid were taken in a sitting position. Increases in the MBR ratio in a supine position were calculated with reference to this baseline. Intraocular pressure (IOP), systemic blood pressure and heart rate in the brachial artery were also recorded. Results: In the ONH, the MBR ratio increased significantly over the baseline after 2 min (104.8 ± 5.0%, p = 0.001) and 4 min (104.4 ± 5.6%, p = 0.005), in a supine position, but decreased to the initial level after only 6 min. In the choroid, on the other hand, while the MBR ratio also increased significantly after 2 min in a supine position (113.7 ± 8.1%, p < 0.001), it kept this significant increase over the time course of 10 min. After 10 min in a supine position, IOP increased significantly (p < 0.001), systolic blood pressure decreased significantly (p < 0.001), but diastolic blood pressure did not change significantly compared to the baseline. (p = 0.07) Conclusions: ONH and choroidal circulation have significantly different hemodynamics in response to posture change in healthy volunteers. This finding suggests that LSFG enables us to assess the autoregulation of BF in the ONH.

Effect of Topical Tafluprost on Optic Nerve Head Blood Flow in Patients With Myopic Disc Type

Purpose:To investigate the effect of topical tafluprost on optic disc blood flow in patients with myopic disc. Materials and Methods:Forty-eight eyes in 24 patients with a myopic disc type (oval shaped) optic disc tilted to the temporal, with a crescent peripapillary atrophy were included in this study. Twenty-eight eyes were diagnosed as normal tension glaucoma and 20 eyes were in normal subjects. None had any treatment for glaucoma. Average age was 45.3±11.9 years. One eye was treated with topical tafluprost and the fellow eye served as the control. Ocular blood flow was measured by laser speckle flowgraphy (LSFG-NAVI) at 30, 60, 90, and 120 minutes after tafluprost administration, and the mean blur rate (MBR) on the optic disc was analyzed. Blood pressure and intraocular pressure (IOP) were recorded. Results:In all subjects, topical tafluprost (a) significantly reduced IOP versus baseline from 60 minutes after treatment (baseline: 15.2±3.4 mm Hg, 60 min: 13.3±3.2 mm Hg, P=0.001, 90 min: 13.3±3.6 mm Hg, P=0.002, 120 min: 13.7±3.4 mm Hg, P=0.007); and (b) significantly increased the MBR versus baseline (60 min: +4.3±6.6%, P=0.008, 90 min: +5.0±4.9%, P<0.001, 120 min: +6.7±7.0%, P<0.001). Conclusions:Topical tafluprost increased MBR in the optic nerve head and significantly reduced IOP, effects that may represent beneficial treatment for glaucoma patients with a myopic disc type.

Calpain-mediated degradation of G-substrate plays a critical role in retinal excitotoxicity for amacrine cells

The role of neuronal N‐methyl‐D‐aspartate (NMDA) receptor‐mediated intracellular signaling has been elucidated in both physiological and pathological conditions. However, the details of relative vulnerability for excitotoxicity remain unknown. Retinal excitotoxicity is involved in various diseases leading to irreversible blindness. Here, we used the visual system and explored the mechanistic details of the NMDA‐elicited intracellular events, especially in the amacrine cells, which are the most vulnerable type of neuron in the retina. G‐substrate, a specific substrate of cyclic guanosine 3′,5′‐monophosphate (cGMP)‐dependent protein kinase, is colocalized with amacrine cells and acts as an endogenous inhibitor of protein phosphatase. To elucidate how G‐substrate was involved in NMDA‐induced amacrine cell death, the immunohistochemical analysis with G‐substrate antibody was performed following NMDA injury. In vivo, NMDA immediately decreased G‐substrate immunoreactivity, and the suppression of calpain activation using ALLN or calpain III, an inhibitor of calpain, blocked this decrease. In vitro, degraded fragments of G‐substrate were detected within 10 min after coincubation of G‐substrate and calpain. Moreover, G‐substrate knockout (G‐substrate−/−) mice were more susceptible to NMDA injury than wild‐type mice. ALLN did not have a neuroprotective effect in G‐substrate−/− mice. These data strongly suggest that calpain‐mediated loss of G‐substrate represents an important mechanism contributing to NMDA‐induced amacrine cell death.

Ulcerative keratitis in patients with rheumatoid arthritis in the modern biologic era: a series of eight cases and literature review

To assess the prevalence, clinical characteristics, treatment, and outcomes of patients who developed ulcerative keratitis (UK) during the course of rheumatoid arthritis (RA) in the modern biologic era.

Fluoroquinolone antibacterial eye drops: effects on normal human corneal epithelium, stroma, and endothelium

Background In vitro studies have suggested the corneal cytotoxicity of third-generation fluoroquinolone levofloxacin (LVFX) and fourth-generation fluoroquinolone moxifloxacin hydrochloride (MFLX) among fluoroquinolone antibacterial eye drops. This study investigated the effects of these two eye drops on the human cornea in vivo. Methods We evaluated 30 healthy adults (19 men and 11 women, 38.3 ± 6.3 years old). Each subject received an LVFX ophthalmic solution 0.5% in one eye and an MFLX ophthalmic solution 0.5% in the other eye three times daily for 7 days. Functional and morphological corneal changes before and after instillation were evaluated through ophthalmic examinations including breakup time of tear film (BUT) as measured by fluorescein staining and DR-1, Schirmer I test, Heidelberg Retina Tomograph II Rostock Cornea Module (HRTII-RCM), specular microscope, and Pentacum examination. Results Both the LVFX and MFLX groups had no significant change in each examination before and after instillation. There was also no statistically significant difference in measurements after the 7-day instillation between the groups. Conclusion Our study results suggest that as with LVFX, MFLX used in a normal clinical setting is unlikely to cause any obvious adverse effects on human normal cornea.

Transparent, resilient human amniotic membrane laminates for corneal transplantation.

This study evaluated a new technique to toughen and optically clarify human amniotic membrane (AM) tissue, which is naturally thin and clouded, and determined the suitability of the altered tissue for corneal transplantation. The technique created a tissue laminate by repeatedly depositing wet layers of AM and dehydrating them, followed by chemical cross-linking to tighten integration at the layer interfaces and within the layers, thereby improving the physical properties of the laminates by increasing light transmittance and mechanical strength. Interestingly, this improvement only occurred in laminates with at least 4 layers. Cross-linking also improved the resistance of the laminates to collagenase degradation, such as occurs in corneal melting. This study also confirmed that the AM tissue was biocompatible by inserting AM monolayers into the corneal stroma of rabbits, and by performing lamellar keratoplasty in rabbits with cross-linked AM laminates. The laminates were sufficiently thick and resilient to need only one set of sutures, whereas in previously described multi-layer AM transplantation technique, each layer required separate sutures. The current findings are a promising advance in the engineering of novel biomaterials and the alteration of existing tissues for medical use.

Efficacy of chandelier illumination for combined cataract operation and penetrating keratoplasty.

Purpose: The aim of this study was to describe a method for non–open-sky continuous curvilinear capsulorhexis (CCC) with chandelier retroillumination for penetrating keratoplasty triple procedure and report its effectiveness in decreasing intraoperative complications and enabling successful primary intraocular lens (IOL) insertion in patients with moderate or dense central corneal opacities. Methods: Seventeen eyes of 17 patients were enrolled in this study, divided into a chandelier group, including 7 eyes of 7 patients, and a nonchandelier group, including 10 eyes of 10 patients. In each group, time to achieve CCC (in seconds), open-sky time (in seconds), and operation time (in minutes) were measured, and the rates of successful CCC completion, rupture of the posterior capsule or zonule of Zinn, and successful IOL insertion were recorded. Results: CCC time was not significantly different in both groups. In the chandelier group, however, open-sky time and operation time were significantly shorter than in the nonchandelier group (1429 ± 67 vs. 2016 ± 354 seconds, and 90.4 ± 3.5 vs. 108.9 ± 10.3 minutes, respectively). In the chandelier group, the rate of successful CCC completion was significantly higher than in the nonchandelier group (86% vs. 30%). The rates of posterior capsule or zonule of Zinn rupture and successful IOL insertion were not significantly different (14% vs. 40%, 14% vs. 10%, and 86% vs. 70%, respectively). Conclusions: Non–open-sky CCC with chandelier illumination has many advantages for penetrating keratoplasty triple procedure compared with open-sky CCC without chandelier illumination.