Shota Kojima

Experimental Optic Cup Enlargement Caused by Endothelin-1–Induced Chronic Optic Nerve Head Ischemia

PURPOSE Vascular insufficiency of the optic nerve head may contribute to glaucomatous optic neuropathy, especially in normal-tension glaucoma. We investigated the effect of chronic optic nerve head ischemia, created by repeated intravitreal injection of endothelin-1 (ET-1), on the morphology and function of the optic nerve. METHODS In pigmented rabbits, we injected ET-1 (10(-6) M, 10 microL) into the posterior vitreous of one eye twice a week for 4 weeks (N = 7). The vehicle for ET-1 was injected into the contralateral eye as a control (N = 7). The subsequent observation period was set at 8 weeks. The microcirculation of the optic nerve head was noninvasively monitored with a laser speckle circulation analyzer. To evaluate the changes of visual function, visual-evoked potentials were recorded. Morphologic changes of the optic nerve head were analyzed with stereography, and the ratio of cup area (CA) to disk area (DA) was measured by calculating the number of pixels in each area with a microcomputer. RESULTS Capillary blood flow in the optic nerve head was continuously below 80% of the baseline throughout the study. The visual-evoked potential latency was significantly delayed in ET-1-treated eyes. The CA/DA ratio was significantly increased relative to baseline in the ET-1 treated eyes. Histologic examination showed axonal loss and demyelination affecting the prelaminar portion of the optic nerve. The intraocular pressure was not significantly different from the control value. CONCLUSION Optic nerve head ischemia could contribute to the enlargement and excavation of the disk cup independent of the intraocular pressure level.

Effects of caffeine on microcirculation of the human ocular fundus.

PURPOSE To determine the effect of caffeine on microcirculation in the human ocular fundus. METHODS The microcirculation in the ocular fundus of 10 healthy volunteers (10 eyes) was studied using a laser speckle tissue circulation analyzer. Caffeine or placebo (100 mg) was administered orally in a double-masked manner. Square blur rate (SBR), a quantitative index of blood flow velocity, was measured in a temporal site of the optic nerve head (ONH) free of surface vessels and in a middle site of the choroid-retina between the ONH and macula. Intraocular pressure (IOP), blood pressure (BP), pulse rate (PR), and central critical fusion frequency (CFF) were also measured. These parameters were measured before and for 2 hours after administration. The area under curve (AUC) of SBR was calculated for each area. Ocular perfusion pressure (OPP) was also calculated from BP and IOP. RESULTS The time-course of change in SBR value showed much individual difference. Caffeine decreased the AUC of SBR in the ONH (P =.0218) as well as in the choroid-retina (P =.0469) significantly. IOP, mean BP, PR, OPP, and central CFF did not change significantly. CONCLUSIONS These results suggest that caffeine may increase blood vessel resistance and decrease blood flow in the human ONH and choroid-retina.

The apical and basal environments of the retinal pigment epithelium regulate the maturation of tight junctions during development.

A culture model has been established to study the gradual development of tight junctions during the embryogenesis of the chick retinal pigment epithelium. This study asks how closely the culture model reflects normal development and how the composition, structure and function of embryonic tight junctions are affected by the apical and basal environments. The study focused on the expression of claudins, the fine-structure of tight junctional strands and the transepithelial electrical resistance. Between embryonic days 7 and 14, patches of junctional strands gradually expanded and coalesced to form a continuous junction, in vivo. Although there was a corresponding increase in claudin expression, different claudins appeared at different times. In culture, the apical and basal environments acted synergistically to promote a continuous network of tight junctions with higher electrical resistance. Independently, pituitary extract or the secretory products of either embryonic fibroblasts or the retina promoted the formation of tight junctions. In combination, three effects were identified. With basally placed fibroblast conditioned medium, apical retinal medium increased transepithelial electrical resistance by affecting structure alone. With basally placed pituitary extract, apical retinal conditioned medium increased transepithelial electrical resistance by affecting structure and by modulating claudin expression in a manner that was consistent with development in vivo. Although embryonic day 7 and 14 cultures in retinal medium exhibited similar structure, the transepithelial electrical resistance of the embryonic day 14 cultures was higher. This higher transepithelial electrical resistance correlated with differences in claudin expression and localization. Therefore, this experimental model can isolate the effects of retinal secretions on structure and claudin expression, and can help us to determine how claudins affect function when structure is held constant.

The first report on intermediate-term outcome of Ex-PRESS glaucoma filtration device implanted under scleral flap in Japanese patients.

Purpose: This paper compares the outcomes of the Ex-PRESS® Glaucoma Filtration Device (Alcon, Fort Worth, TX) implant observed in Japanese patients for 1 year with those of patients undergoing trabeculectomy. Patients and methods: The subjects comprised ten eyes of ten cases with open-angle glaucoma for which filtration surgery using Ex-PRESS (P-50) was performed by one operator from February 2008 and observed for at least 1 year (Ex-PRESS Group), and eleven eyes of eleven cases for which trabeculectomy was performed by the same operator (TE Group). For both groups, mitomycin C was used and a scleral flap was created after a fornix-based incision of the conjunctiva. Results: Hypotony and choroidal detachment were observed as early postoperative complications during a 1-week period in one-third of the cases in the TE Group, and failing vision in about 45%, while these were seen in fewer cases in the Ex-PRESS Group. No significant difference in intraocular pressure (IOP) was observed during the period, but IOP variations on the day following the surgery were obviously narrower in the Ex-PRESS Group than in the TE Group. Visual acuity was significantly poorer from 1 week to 3 months in the TE Group while it was stable in the Ex-PRESS Group. The Ex-PRESS Group had fewer cases of laser suture lysis and fewer administrations of glaucoma eyedrop, and no cases of progression in the stage of visual field defect. Conclusion: Filtration surgery using the Ex-PRESS is unlikely to cause early complications in Japanese patients. Similarly to the trabeculectomy, the intermediate-term control of IOP showed favorable results.

Changes in optic nerve head blood flow induced by the combined therapy of latanoprost and beta blockers

Purpose  To assess the effects of combined therapy with latanoprost and beta blockers on optic nerve head (ONH) blood flow in normal‐tension glaucoma (NTG) patients.

Clinical results of selective laser trabeculoplasty in open-angle glaucoma in Japanese eyes: comparison of 180 degree with 360 degree SLT.

PurposeTo evaluate the efficacy of selective laser trabeculoplasty (SLT) in the adjunctive treatment of medically diagnosed open-angle glaucoma and to compare the difference in intraocular pressure (IOP) lowering effects between 180-degree and 360-degree SLT. MethodsThis study is a retrospective consecutive chart review of open-angle glaucoma patients who had undergone first-time SLT from January of 2005 to July of 2007. All the patients had primary open-angle glaucoma or pseudoexfoliation glaucoma under medical treatment and followed for at least 3 months after the procedure. The IOP reduction and treatment success were compared with the 2 treatment types. ResultsTwenty-nine patients underwent 180-degree SLT (35 eyes) and 25 patients underwent 360-degree SLT (34 eyes). The average follow-up was 19.5 months (range 3 to 36) for 180-degree group and 17.9 months (range 3 to 36) for 360-degree group. During the follow-up period, the 360-degree SLT group showed significantly lower posttreatment IOP at each follow-up point relative to pretreatment IOP, and its IOP reduction rate stayed statistically higher than the 180-degree group. We found a positive correlation between the pretreatment IOP and the IOP reduction rate for 360-degree SLT. The lower the pretreatment IOP was, the lower IOP reduction rate became. A Kaplan-Meier survival analysis showed higher success rates after 360-degree SLT than after 180-degree SLT. ConclusionsThe 360-degree SLT was shown to be more effective than180-degree SLT for intermediateterm reduction in IOP of Japanese patients with open-angle glaucoma as an adjunctive treatment protocol.

Long-term effect of topically applied isopropyl unoprostone on microcirculation in the human ocular fundus.

PURPOSE To investigate the long-term effect of 0.12% isopropyl unoprostone (Rescula) on microcirculation in the human ocular fundus. METHODS A laser speckle tissue circulation analyzer was used to measure normalized blur (NB), a quantitative index of blood flow velocity, in the optic nerve head (ONH) and choroid-retina before and 4.5 hours after the instillation of a placebo into both eyes of 11 healthy volunteers. The intraocular pressure (IOP), blood pressure, and pulse rate were also recorded in this control experiment. Thereafter, a drop of unoprostone or a placebo was instilled into each eye in a double-blind manner twice a day for 21 days to form treated and untreated groups. RESULTS After 21 days, the NB values in the ONH and choroid-retina had increased significantly and the IOP had decreased significantly in the unoprostone-treated eyes. Ocular perfusion pressure showed no significant change. CONCLUSIONS These results suggest that long-term application of unoprostone can increase microcirculatory blood flow in the human ocular fundus, probably due to a reduction in vascular resistance.

Effect of the Consumption of Ethanol on the Microcirculation of the Human Optic Nerve Head in the Acute Phase

PURPOSE The effect of the consumption of ethanol on the circulation of the optic nerve head (ONH) in the human eye in the acute phase and its mechanism were studied. METHODS Eleven volunteers drank a bottle of beer (633 ml) with or without ethanol (29.5 g). Normalized blur (NB), a quantitative index of blood flow velocity, was measured in the temporal site of the ONH. NB, blood pressure (BP) and pulse rate (PR) were measured before, immediately after, and every 15 minutes for 90 minutes after consumption. Intraocular pressure (IOP) and plasma ethanol concentration were measured before, and 30 and 90 minutes after consumption. Genotyping of the aldehyde dehydrogenase (ALDH) 2 gene was also performed. RESULTS NB in the ONH increased significantly from 15 to 45 minutes after consumption of ethanol and the maximum increase was 14% at 15 minutes. IOP was lowered at 90 minutes after consumption, but it was not significant. Mean BP was lowered significantly after 60 minutes. PR and ocular perfusion pressure did not change. A significant correlation was found between plasma ethanol concentration at 30 minutes and maximum NB. NB in the ALDH 2-deficient group was significantly larger from 15 to 45 minutes after consumption than in the proficient group. CONCLUSION It appeared that the consumption of ethanol can increase the blood flow in the human ONH in the acute phase through decreased resistance in blood vessels induced by acetaldehyde, a metabolite of ethanol.

Involvement of nitric oxide in the ocular hypotensive action of nipradilol.

Purpose. To evaluate the role of nitric oxide (NO) in the mechanism of the ocular hypotensive action of nipradilol, a ß-blocker with a 1 -blocking activity. Methods. Change in intraocular pressure (IOP) of albino rabbits was measured after a single application of carboxy-PTIO (c-PTIO), an NO trapping agent. Next, IOP change was measured every hour for 5 hours after the instillation of 0.25% nipradilol into one of the eyes with and without c-PTIO pretreatment of both eyes. IOP change induced by desnitro-nipradilol was also examined. The outflow facility and uveoscleral outflow were determined by two-level constant pressure and anterior chamber perfusion methods before and at 3 hours after the application of nipradilol with and without c-PTIO pretreatment. Results. Topical administration of c-PTIO showed no significant effect on IOP. Unilateral instillation of nipradilol reduced IOP significantly compared with control eyes with a maximum reduction of 3.6 mmHg and effect duration of 3 hours. Pretreatment with c-PTIO partially inhibited the reduction during an earlier period (1~2 hours) and completely at 3 hours. IOP change by desnitro-nipradilol was similar to that by nipradilol with c-PTIO pretreatment. Nipradilol increased both outflow facility and uveoscleral outflow at 3 hours, whereas pretreatment with c-PTIO inhibited both of these outflows. Conclusions. Results indicate that ocular hypotensive action by nipradilol during the relatively late period may be mainly due to enhancement of aqueous humor outflow by NO at least in the rabbits.

Improving effects of topical administration of iganidipine, a new calcium channel blocker, on the impaired visual evoked potential after endothelin-1 injection into the vitreous body of rabbits

PURPOSE To investigate the effect of topical iganidipine, a new dihydropyridine derivative calcium channel blocker, on impairment of the ocular circulation caused by endothelin-1 (ET-1), we examined modification of the effect of ET-1 on visual-evoked potential (VEP) in albino rabbits. METHODS To clarify whether VEP could be used to indicate the extent of ocular circulatory impairment, we evaluated the dose dependency of changes in VEP over 2 hours after intravitreal injection of 3 ET-1 doses (1.0, 3.3, or 10 pmol) and the vehicle. Then modification of the effect of ET-1 on the VEP by iganidipine was examined. One hour after the topical instillation of 0.1% iganidipine (20 microl) or its vehicle, 10 pmol of ET-1 was injected into the vitreous in rabbits. The VEP was measured for 2 hours after ET-1 application, and the response was compared between the eyes with iganidipine and vehicle pretreatment. RESULTS Intravitreal injection of ET-1 dose-dependently reduced the VEP amplitude. Topical administration of 0.1% iganidipine significantly suppressed the reduction of VEP amplitude for the entire 2-hour monitoring period after intravitreal injection of 10 pmol ET-1. There was no significant change of the systemic blood pressure as well as intraocular pressure after topical administration of iganidipine. CONCLUSIONS Iganidipine eyedrops may be useful for the treatment of ischemic retinal and optic nerve disorders related to abnormal ET-1 production for the maintenance of visual function.