Yoshiaki Kiuchi

Circadian intraocular pressure management with latanoprost: diurnal and nocturnal intraocular pressure reduction and increased uveoscleral outflow.

Based on their mechanism of action, the most frequently used ocular hypertensive agents, the beta-blockers, cannot be assumed to reduce IOP during sleep. The need for drugs that reduce IOP around-the-clock is underscored, however, by the fact that inadequate nocturnal ocular perfusion pressure is considered to be one of the likely causes of glaucomatous optic neuropathy especially in some cases of normal tension glaucoma. The studies reviewed here demonstrate that latanoprost, a new ocular hypotensive prostaglandin F2 alpha analogue, applied once a day at a concentration of 0.005%, maintains a statistically highly significant IOP reduction around-the-clock. The magnitude of this IOP reduction was found to be essentially identical during the day and at night, both in patients maintained on timolol and in those not receiving other glaucoma medication. Latanoprost-induced IOP reduction was also found to be associated with increased uveoscleral outflow in normotensive volunteers, both during the day and at night. These circadian studies suggest that this new ocular hypotensive agent can be expected to be particularly useful for the medical management of some forms of glaucoma, such as normal tension glaucoma, when the cause of the glaucomatous damage cannot be linked specifically to diurnal IOP abnormalities.

Vascular risk factors in glaucoma: a review

Glaucoma, one of the major causes of blindness in the world, is a progressive optic neuropathy. Elevated intraocular pressure is a well‐known major risk factor for glaucoma. In addition, there is growing evidence that vascular factors may play a role in glaucoma pathogenesis. Systemic (e.g. hypertension, diabetes) and ocular vascular factors (e.g. ocular blood flow, ocular perfusion pressure) have been assessed for associations with glaucoma. However, direct and convincing evidence for primary mechanisms of glaucoma is still lacking. The aim of this review is to summarize the evidence implicating vascular factors in the pathogenesis of glaucoma, with particular emphasis on the role of ocular blood flow and ocular circulation as risk factors for primary open angle glaucoma.

A polymorphism of LOC387715 gene is associated with age-related macular degeneration in the Japanese population

Age-related macular degeneration (AMD) is one of the leading causes of blindness among older adults in developed countries and also in Japan. Previous research suggests that AMD is etiologically a complex disease, caused by multiple genes and environmental factors. Association studies have identified that a complement factor H gene (CFH) variant is a major risk factor for AMD in Caucasians. However, we and two other groups have reported no association between CFH and AMD in the Japanese population. Recent studies have suggested that LOC387715 on chromosome 10q26 may be the second major risk loci for AMD in Caucasians. In this study, we examined the association between LOC387715 and AMD in Japanese, and our results show that polymorphism of the LOC387715 gene is associated with AMD in Japanese as well as in Caucasians. Our data show a disease odds ratio of 6.20 (95% CI: 2.87-13.40) conferred by homozygosity for risk alleles at LOC387715 compared with the non-risk genotype. A polymorphism of LOC387715 gene is associated with AMD in the Japanese population.

Comparison of drug permeabilities across the blood–retinal barrier, blood–aqueous humor barrier, and blood–brain barrier

Drugs vary in their ability to permeate the blood-retinal barrier (BRB), blood-aqueous humor barrier (BAB), and blood-brain barrier (BBB) and the factors affecting the drug permeation remain unclear. In this study, the permeability of various substances across BRB, BAB, and BBB in rats was determined using the brain uptake index (BUI), retinal uptake index (RUI), and aqueous humor uptake index (AHUI) methods. Lipophilic substances showed high permeabilities across BBB and BRB. The RUI values of these substances were approximately four-fold higher than the BUI values. The AHUI versus lipophilicity curve had a parabolic shape with AHUI(max) values at log D(7.4) ranging from -1.0 to 0.0. On the basis of the difference on the lipophilicities, verapamil, quinidine, and digoxin showed lower permeability than predicted from those across BBB and BRB, whereas only digoxin showed a lower permeability across BRB. These low permeabilities were significantly increased by P-glycoprotein inhibitors. Furthermore, anion transporter inhibition increased the absorption of digoxin to permeate into the retina and aqueous humor. In conclusion, this study suggests that efflux transport systems play an important role in the ocular absorption of drugs from the circulating blood after systemic administration.

The applicability of ganglion cell complex parameters determined from SD-OCT images to detect glaucomatous eyes.

Purpose:To determine whether the thicknesses of the different parameters of the ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer can be used to differentiate eyes with glaucoma from normal eyes. Methods:Two hundred sixty-one eyes, including 68 normal eyes and 32 preperimetric glaucoma, 81 early glaucoma, and 80 advanced glaucoma were analyzed in the present study. The thicknesses of the GCC and retinal nerve fiber layer were measured using RTVue spectral-domain optical coherence tomographic (SD-OCT) images. The area under the receiver operating characteristic (AUROC) curve and sensitivities at fixed specificities were calculated for each parameter. A logistic regression analysis was used to determine the risk factors for glaucoma. Results:The 2 largest AUROC curves for all glaucoma stages were those for the GCC parameters. The global loss volume (GLV) was always one of the 2 highest values of the AUROC curve. The GLV also had the highest sensitivity at a fixed specificity to identify glaucoma at early and advanced stage. The focal loss volume (FLV) had the largest AUROC curve value and the highest sensitivity at a fixed specificity for advanced glaucoma. The logistic regression analysis showed that the GLV was one of the factors that predicted preperimetric glaucoma [odds ratio (OR)=1.74] and early glaucoma (OR=1.22), whereas the FLV was useful for detecting advanced glaucoma (OR=2.32). Conclusions:The SD-OCT-derived macular GCC parameters can be used to detect preperimetric and perimetric glaucoma. The new GCC parameters, GLV and FLV, performed well in discriminating glaucomatous eyes from normal eyes.

Trabeculectomy with Mitomycin C for Treatment of Neovascular Glaucoma in Diabetic Patients

Background: To assess the efficacy and to determine the risk factors of trabeculectomy with mitomycin C (MMC) in eyes with neovascular glaucoma (NVG) secondary to diabetic retinopathy. Methods: Kaplan-Meier survival analysis of the surgical outcome was performed on 35 eyes with NVG. Age, extent of peripheral anterior synechia, surgical history (cataract, glaucoma, vitrectomy), and concurrent retinal cryotherapy were evaluated to determine factors influencing the surgical outcome. The main criterion for success was a postoperative intraocular pressure (IOP) of ≤21 mm Hg. Results: The cumulative probability of success was 67.0% at 1 year and 61.8% after 2 to 3 years. The surgical outcome was significantly better in patients without a previous vitrectomy (p = 0.03). Extensive preoperative peripheral anterior synechia was also a risk factor for surgical failure (p = 0.013). Conclusions: Trabeculectomy with MMC can effectively reduce the elevated IOP associated with NVG. The extent of peripheral anterior synechia and a history of vitrectomy are significant negative predictors of surgical outcome.

Macular Choroidal Thickness and Volume in Healthy Pediatric Individuals Measured by Swept-Source Optical Coherence Tomography

PURPOSE We evaluated the choroidal thickness and volume in healthy pediatric individuals by swept-source optical coherence tomography (SS-OCT) and compared the findings to those of adults. METHODS We examined 100 eyes of 100 healthy pediatric volunteers (3-15 years) and 83 eyes of 83 healthy adult volunteers (24-87 years) by SS-OCT with a tunable long wavelength laser source. The three-dimensional raster scan protocol was used to construct a choroidal thickness map. When the built-in software delineated an erroneous chorioscleral border in the B-scan images, manual segmentation was used. RESULTS The central choroidal thickness and volume within a 1.0-mm circle were significantly larger in the children (260.4 ± 57.2 μm, 0.205 ± 0.045 mm(3)) than in the adults (206.1 ± 72.5 μm, 0.160 ± 0.056 mm(3), both P < 0.0001). In the children, the mean choroidal thickness of the nasal area was significantly thinner than that of all other areas (P < 0.005). Pediatric choroidal thinning with increasing age in the central area was faster than that in the outer areas. Stepwise regression analysis showed that the axial length and body mass index had the highest correlation with the choroidal thickness (R(2) = 0.313, P < 0.0001). CONCLUSIONS The macular choroidal thickness and volume in the pediatric individuals were significantly larger than those in the adults. The pediatric choroidal thinning with increasing age is more rapid in the central area. Pediatric choroidal thickness is associated with several systemic or ocular parameters, especially the axial length and body mass index. These differences should be remembered when the choroidal thickness is evaluated in pediatric patients with retinochoroidal diseases.

Ultrasound Biomicroscopic Study of Ciliary Body Thickness After Topical Application of Pharmacologic Agents

PURPOSE To examine the changes in ciliary body thickness after topical application of pilocarpine, cyclopentolate hydrochloride, and PhXA41, a prostaglandin F2alpha analog. METHOD We used high-frequency Humphrey UBM840 ultrasound biomicroscope to examine 36 healthy young Japanese subjects. RESULTS The mean ciliary body thickness increased from 0.67 +/- 0.07 mm to 0.073 +/- 0.08 mm (P < .01) after application of 2% pilocarpine; 1% cyclopentolate hydrochloride and 0.005% PhXA41 decreased the mean ciliary body thickness from 0.75 +/- 0.07 mm to 0.69 +/- 0.05 mm (P < .05) and from 0.78 +/- 0.06 mm to 0.75 +/- 0.06 mm (P < .01), respectively. CONCLUSIONS Our ultrasound study clearly indicates that pilocarpine increased comparative thickness of the ciliary body by 8.3%, whereas PhXA41 decreased comparative thickness by 3.3% in a manner similar to cyclopentolate hydrochloride.

Contact-Based Stiffness Sensing of Human Eye

Goldmann applanation tonometry is commonly used for measuring intraocular pressure (IOP) to diagnose glaucoma. However, the measured IOP by conventional applanation tonometry is valid only under the assumption that all subjects have the same structural eye stiffness. This paper challenges in vivo measurement of eye stiffness with a noninvasive approach and investigates individual differences of eye stiffness. Eye stiffness is defined by the applied force and displacement of the cornea. The displacement is detected based on captured images by a high resolution camera. The experimental results show that the measured stiffness nicely matches the analytical result that is derived from a simple spherical deformation model with an internal pressure. However, some subjects have different eye stiffness even with the same IOP. IOP with abnormal stiffness may be over/underestimated by conventional applanation tonometry. The proposed eye stiffness measurement can help detect the misestimated eye and it contributes to the early detection of glaucoma.

Incidence of Retinal Vein Occlusion at the Glaucoma Clinic of Hiroshima University

We prospectively surveyed the incidence of retinal vein occlusion (RVO) at the glaucoma clinic of Hiroshima University between 1986 and 1991. Among 433 glaucoma patients, 18 (4.2%) subsequently presented with RVO, 9 had central retinal vein occlusion (CRVO) and 9 exhibited branch retinal vein occlusion (BRVO). Seven of 87 (8.1%) patients with primary angle closure glaucoma exhibited RVO, showing the highest incidence among glaucoma types. The incidence of RVO detected by the general outpatient clinic was 0.59% during the same period. The BRVO/CRVO ratio in the glaucoma clinic was 1.0, while it was 4.3 in the general outpatient clinic. Glaucoma is an important risk factor for the development of RVO, especially CRVO.