[Show abstract][Hide abstract] ABSTRACT: Purpose:
To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used.
Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katra Phytochem). The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured.
The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. "retinal responders", who had an increase of both MPOD levels and serum lutein concentrations (n = 13), "retinal non-responders", who had only increased serum concentrations and no change in MPOD levels (n = 20), and "retinal and serum non-responders", who had neither MPOD level nor plasma concentration increases (n = 3). The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133). Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in contrast sensitivity.
No statistically significant differences could be detected for MPOD levels and serum lutein concentrations between the two investigated lutein supplement formulations. Responses to lutein supplementation regarding MPOD levels and serum lutein concentrations varied between subjects. Subjects with lower MPOD levels at baseline responded well to lutein supplementation. However, since the number of subjects was low, a further study with more subjects is needed to prove that subjects with low MPOD levels will benefit from lutein supplementation.
PLoS ONE 10/2015; 10(10):e0139257. DOI:10.1371/journal.pone.0139257 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. We reported previously that the level of systemic antioxidative capacity is lower in patients with open-angle glaucoma than controls without glaucoma. Here, we assessed the correlation between IOP and systemic levels of prooxidants and antioxidants by analyzing the blood biochemistry in patients with glaucoma.
Peripheral blood samples were collected from Japanese patients with primary open-angle glaucoma (n = 206), exfoliation syndrome (n = 199), and controls (n = 126). Serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. To test the possible effect of oxidative stress on IOP levels, the patients were classified into one of four groups (Q1, Q2, Q3, and Q4, with Q1 having the lowest IOP) based on the quartile value of IOP. For this classification, the known highest IOP value in both the right and left eyes was regarded as each subject's IOP. For comparisons among the IOP groups, the differences were calculated using one-way analysis of variance followed by post-hoc unpaired t-tests. To adjust for differences in demographic characteristic distributions, the dROM, BAP, and SH test values were compared among the IOP groups using multiple logistic regression analysis; the odds ratio (OR) of each variable was calculated with the Q1 group as the reference.
The dROM and the SH levels did not differ significantly (p = 0.6704 and p = 0.6376, respectively) among the four IOP groups. The BAP levels differed significantly (p = 0.0115) among the four IOP groups; the value was significantly lower in the Q4 group (1,932 μmol/L) compared with the Q1 (2,023 μmol/L, p = 0.0042) and Q2 (2,003 μmol/L, p = 0.0302) groups and significantly lower in the Q3 group (1,948 μmol/L) than the Q1 (p = 0.0174) group. After adjustment for differences in various demographic characteristics, lower BAP values were significantly associated with the classification into higher IOP groups (Q3 group, p = 0.0261 and OR = 0.06/range; Q4 group, p = 0.0018 and OR = 0.04/range). The dROM and SH values did not reach significance in any comparisons.
Lower systemic antioxidant capacity measured by ferric-reducing activity is involved in the pathogenesis of open-angle glaucoma via its roles in IOP elevation.
PLoS ONE 07/2015; 10(7):e0133582. DOI:10.1371/journal.pone.0133582 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To evaluate some clinically important features of benzalkonium chloride (BAK) toxicity by comparing tafluprost with 0.001% BAK and travoprost preserved with SofZia applied to the ocular surface of the eyes with glaucoma. Methods: This was a prospective, randomized, observer unmasked, multicenter crossover trial. A total of 195 patients were randomized and 174 patients completed the study at 19 clinics between November 2011 and August 2012. Topical BAK-preserved tafluprost or SofZia-preserved travoprost was newly administered or continued. Superficial punctate keratopathy (SPK), tear break-up time (BUT), the conjunctival hyperemia score, and intraocular pressure (IOP) were compared at the baseline visit, 4, and 12 weeks after the start of therapy. The eye drops were switched to another eye drop after 12 weeks of observation. Results: The total SPK and conjunctival hyperemia scores were significantly lower in the tafluprost compared with those in the travoprost phase (both P=0.038). There were no significant differences in the SPK scores of the superior area (P=0.679), central area (P=0.089), inferior area (P=0.090), and tear BUT (P=0.271). The IOP-lowering effects were similar (P=0.155). Conclusions: SPK, hyperemia score, and tear BUT while using tafluprost with 0.001% BAK were not inferior compared with those caused by travoprost with SofZia.
Journal of Ocular Pharmacology and Therapeutics 02/2015; 31(3). DOI:10.1089/jop.2014.0104 · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of Ex-PRESS miniature glaucoma shunt obstruction resulting from progressive iris synechial formation after transient anterior chamber shallowing.
A 68-year-old woman with pseudoexfoliation glaucoma in her right eye underwent filtration surgery with implantation of the Ex-PPESS shunt (model P-50, Alcon Japan, Tokyo, Japan) in combination with intra-surgical 0.04% mitomycin C use. After the anterior chamber injection of viscoelastic material and 100% sulfur hexafluoride gas for treatment of early postoperative over filtration, the intraocular pressure (IOP) was controlled between 9 and 12 mmHg. On postoperative day 121, gonioscopy showed that synechial formation around the shunt obstructed the axial port leaving the relief port opened. On postoperative day 274, the intraocular pressure increased to 40 mmHg and synechiae obstructed both the axial and relief ports. Dispersion of iris tissue by neodymium:yttrium-aluminium-garnet (Nd:YAG) laser (2 mJ, one shot to each port) opened both ports and immediately lowered the IOP, leaving peripheral anterior synechiae around the shunt. Up to postoperative day 400, the IOP was controlled between 13 and 15 mmHg, and the cystic bleb was maintained.
The synechiae formed gradually extends around the shunt's shaft and can result in later external obstruction of the relief port. The current case requires further follow-up since synechiae remaining around the shaft can cause future obstruction. We emphasize the fact that, if the iris synechiae to the shunt once formed, it can progress and obstruct the shunt ports later.
[Show abstract][Hide abstract] ABSTRACT: Purpose
To elucidate Japanese trends for perioperative disinfection and antibiotic selection during cataract surgeries.
Perioperative iodine use and antibiotic prophylaxis for cataract surgery were surveyed in eight regions in Japan by mail or through interviews from February 1 to March 1, 2014.
We surveyed 572 surgeons, of whom 386 (67%) responded. Most of the surgeons (94%) used iodine compounds before surgery for periocular skin disinfection (povidone–iodine [PI]: 79%; polyvinyl alcohol-iodine [PAI]: 15%) or conjunctival disinfection (85%; PI: 36%; PAI: 49%). Preoperative conjunctival iodine was primarily used as an eye wash (irrigation: 95%) and less often as an eye drop (5%). It was determined that 31% of surgeons waited 30 seconds or more between periocular disinfection and conjunctival disinfection. During surgery, 14% of surgeons used iodine several times, including immediately before intraocular lens insertion, and 7% used the Shimada technique (repeated iodine irrigation). Preoperative antibiotic eye drops were used by 99% of surgeons, and antibiotics were added to the irrigation bottle by 22%. The surgeons reported use of subconjunctival antibiotic injections (23%), antibiotic ointments (79%), and intracameral antibiotics (7%: 22 moxifloxacin; 6 levofloxacin). All surgeons prescribed postoperative eye drops, with 10% initiating the drops on the day of surgery.
Iodine compounds are commonly used preoperatively, but few institutions use iodine compounds intraoperatively, particularly with repeated application. The selection of antibiotic administration and disinfection technique has to be at the surgeon’s discretion. However, intracameral antibiotic and intraoperative iodine compound use are techniques that should be widely recognized.
[Show abstract][Hide abstract] ABSTRACT: PurposeA possible association has been reported between exfoliation syndrome (EX) and various ocular and systemic vascular disorders; however, it is unclear if there is an association between EX and central retinal vein occlusion (CRVO). Because latent deposits of exfoliation materials might not be recognized during slit-lamp examination, an ocular biopsy is required to establish a precise diagnosis. We evaluated a possible association between EX and CRVO using lysyl oxidase-like 1 (LOXL1) gene variants as alternative markers for EX.Methods
The allelic and genotypic frequencies of three LOXL1 variants (rs1048661, rs3825942, and rs2165241) were determined in 68 consecutive Japanese patients with CRVO [15 with exfoliation syndrome (EX+) and 53 without exfoliation syndrome (EX−)] and 90 control patients with cataract without EX (CT).ResultsThe frequencies of the rs1048661 and rs3825942 variants showed borderline difference between the CRVO and CT groups (p = 0.04085 and p = 0.06088, respectively, for allelic frequencies, and p = 0.06838 and p = 0.03482, respectively, for genotypic frequencies). Compared with the CT group, subgroup analysis showed that the CRVO EX+ group had significant differences in the allelic and genotypic frequencies of rs1048661 (p = 0.0006447 and p = 0.0001392, respectively) and had borderline differences in the allelic and genotypic frequencies of rs3825942 (p = 0.03403 and p = 0.07341, respectively), while the CRVO EX− group did not (p = 0.1324–0.6306). Subgroup analysis showed that the frequencies of rs2165241 did not differ between the CRVO and CT groups.Conclusions
When the LOXL1 variants were used as disease markers for clinically undetectable EX, there was no association between CRVO and EX. The results suggested that the LOXL1 variants, which are well-established markers for EX, are not likely genetic markers for CRVO in Japanese subjects.
[Show abstract][Hide abstract] ABSTRACT: Purpose
The Glaucoma Stereo Analysis Study (GSAS), a cross sectional multicenter collaborative study, used a stereo fundus camera to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients and investigated the relationships between these parameters and patient characteristics.
Subjects and Methods
The study included 187 eyes of 187 subjects with primary open angle glaucoma or normal tension glaucoma (male: female = 100: 87, age = 61±9 years). Stereo pairs of ONH photographs were made with a stereo fundus camera (nonmyd WX). ONH morphological parameters were calculated with prototype analysis software. In addition to 35 standard parameters, we defined three novel parameters: disc tilt angle, rim decentering, and the absolute value of rim decentering. The correlation between each parameter and patient characteristics was analyzed with Spearman's rank correlation coefficient.
Patient characteristics included refractive error of −3.38±3.75 diopters, intraocular pressure (IOP) of 13.6±2.6 mmHg, and visual field mean deviation (MD) of −4.71±3.26 dB. Representative ONH parameters included a horizontal disc width of 1.66±0.28 mm, vertical disc width of 1.86±0.23 mm, disc area of 2.42±0.63 mm2, cup area of 1.45±0.57 mm2, and cup volume of 0.31±0.22 mm3. Correlation analysis revealed significant negative associations between vertical cup-to-disc ratio (0.82±0.08) and MD (r = −0.40, P<0.01) and between disc tilt angle (10.5±12.5 degrees) and refractive error (r = −0.36, P<0.01). Seventy-five percent of the eyes had a positive value for rim decentering (0.30±0.42), indicating that rim thinning manifested more often as an inferior lesion than a superior lesion.
We used stereoscopic analysis to establish a database of ONH parameters, which may facilitate future studies of glaucomatous changes in ONH morphology.
PLoS ONE 06/2014; 9(6):e99138. DOI:10.1371/journal.pone.0099138 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To estimate the melatonin suppression index (MSI), which may reflect the nonvisual photoreception function, through commercially available foldable, clear and yellow-tinted intraocular lenses (IOLs).
The MSIs for 13 IOL models (6 clear IOLs, 7 yellow-tinted IOLs) with three lens powers were calculated based on previously reported data about the melatonin suppression spectrum, spectral intensity of a 20-W white fluorescent lamp and spectral transmission of IOLs in wavelengths from 300 to 800 nm. The models tested were the SA60AT and SN60AT (Alcon Japan); the VA-60BBR, YA-60BBR, and NM-1 (Hoya); the AU6K and AN6K (Kowa); the N4-18B and N4-18YG (Nidek); the X-60 and NX-60 (Santen); and the KS-3Ai and KS-AiN (Staar Japan).
The MSIs of the clear IOLs ranged from 1.12 to 1.18 mW cm(-2) sr(-1) and those of the yellow-tinted IOLs from 0.74 to 1.01 mW cm(-2) sr(-1). All yellow-tinted IOLs had significantly lower MSIs (P < 0.0001-0.0021) than the clear IOLs; the %MSI cutoff values for yellow-tinted IOLs compared to the clear IOLs were 11.4-36.2 %. The MSIs of the six clear IOLs did not differ based on lens powers (P = 0.2159-0.6144). Except for one IOL model, all yellow-tinted IOLs had a lower MSI with higher lens powers compared to those with lower lens powers (P < 0.0001-0.0055). Compared to phakic eyes (MSI, 1.03 mW cm(-2) sr(-1)), the MSIs of the clear IOLs were higher (%MSI cutoff, -14.6 to -8.4 %), whereas those of the yellow-tinted IOLs were lower (2.6-28.1 %). Compared to aphakic eyes (MSI, 1.21 mW cm(-2) sr(-1)), the MSIs of the clear (2.1-7.4 %) and yellow-tinted (16.7-38.6 %) IOLs were lower.
Yellow-tinted IOLs absorb more circadian rhythm-associated light than clear IOLs. The difference in the lens power is significantly related to the MSI value in some yellow-tinted IOLs. To correlate the current data with the clinical relevance of these findings, the percent loss of the MSI leading to a circadian rhythm disorder needs to be clarified.
Japanese Journal of Ophthalmology 04/2014; 58(4). DOI:10.1007/s10384-014-0320-x · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Macular pigment is a defense system against phototoxic damage of the retina by visible light. It is still under debate whether or not macular pigment optical density (MPOD) levels decline with age, because the age effect varied depending on the technique used to measure MPOD levels. Resonance Raman spectroscopy (RRS) is an objective method to measure MPOD, and studies using RRS showed a drastic age-related decline of MPOD levels; however, since RRS measurements are influenced by cataracts, it has been argued that the age-related decline of RRS measurements is an artifact from lens changes in aged subjects. In the present study, MPOD levels were measured with RRS in pseudophakic eyes, and the effects of age and other factors on MPOD levels were investigated.
The subjects included 144 patients with no fundus disorders who received cataract surgery with untinted intraocular lens implantation. MPOD levels were measured in 144 eyes using integral RRS 1 day post surgery. Factors potentially associated with MPOD levels such as age, gender, smoking habits, body mass index, diabetes, glaucoma, axial length, pupil diameter, spherical equivalent refractive error, and foveal thickness were examined by multiple regression analysis.
The macular pigment RRS levels ranged from 776 to 11,815 Raman counts, with an average level of 4,375 ± 1,917 (standard deviation [SD]) Raman counts. Multiple regression analysis revealed that age and axial length were significantly correlated with low MPOD values (regression coefficient of -59 for age and -404 for axial length, respectively). No significant correlations were observed for other factors.
After removing the potentially confounding effect of age-related lens yellowing on the RRS measurements, age remained a significant patient parameter for lowered MPOD levels. MPOD levels were found to decline by more than 10 % each decade. Axial length was also a negative predictor of MPOD levels. Since the present study included only patients aged 50 years and older, the effects of age and other factors on MPOD levels for younger subjects remain unknown.
Albrecht von Graæes Archiv für Ophthalmologie 03/2014; 252(11). DOI:10.1007/s00417-014-2574-x · 1.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report the reproducibility profile of optic nerve head parameters obtained by computer software-assisted fundus photoplanimetry.
Fundus photographs obtained during a population-based health survey (Sakurae Study) were planimetrically analyzed using newly developed computer software, CDSketch. The parameters assessed included vertical and horizontal cup-to-disc (C/D) ratios, superior and inferior rim-to-disc (R/D) ratios, disc and cup vertical-to-horizontal (V/H) ratios, and disc-macular distance-to-disc diameter (DM/DD) ratio. For intraobserver and interobserver agreement assessments, we calculated the coefficients of variation (CVs) and intraclass correlation coefficients (ICCs) of the mean of three measurements obtained by one observer and a one-time measurement by three observers, respectively.
The intraobserver CVs were between 2.4 % (DM/DD ratio) and 11.0 % (inferior R/D ratio), and the ICCs were between 0.868 (cup V/H ratio) and 0.976 (DM/DD ratio); all intraobserver ICCs had almost perfect agreement (>0.81). The interobserver CVs were between 2.6 % (disc V/H ratio) and 18.0 % (inferior R/D ratio), and the ICCs were between 0.762 (cup V/H ratio) and 0.930 (DM/DD ratio); the interobserver ICCs were categorized as substantial (0.61-0.80) for the inferior R/D and cup V/H ratios and as almost perfect for the other five parameters.
The consistent profiles of the planimetric parameters suggest the suitability of software-assisted photoplanimetry for assessing optic disc characteristics in glaucoma clinical study and practice.
Japanese Journal of Ophthalmology 10/2013; 58(1). DOI:10.1007/s10384-013-0280-6 · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oxidative stress has been suspected of contributing to the pathogenesis of pterygia. We evaluated the immunohistochemical localization of the markers of oxidative stress, that is, the proteins modified by 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE), which are reactive aldehydes derived from nonenzymatic oxidation of n-3 and n-6 polyunsaturated fatty acids, respectively. In the pterygial head, labeling of 4-HHE- and 4-HNE-modified proteins was prominent in the nuclei and cytosol of the epithelium. In the pterygial body, strong labeling was observed in the nuclei and cytosol of the epithelium and proliferating subepithelial connective tissue. In normal conjunctival specimens, only trace immunoreactivity of both proteins was observed in the epithelial and stromal layers. Exposures of ultraviolet (330 nm, 48.32 ± 0.55 J/cm(2)) or blue light (400 nm, 293.0 ± 2.0 J/cm(2)) to rat eyes enhanced labeling of 4-HHE- and 4-HNE-modified proteins in the nuclei of conjunctival epithelium. Protein modifications by biologically active aldehydes are a molecular event involved in the development of pterygia.
Oxidative Medicine and Cellular Longevity 05/2013; 2013(7):602029. DOI:10.1155/2013/602029 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To report the efficacy of systemic prostaglandin E1 (PGE1) monotherapy for treating acute central retinal artery occlusion (CRAO).
The best-corrected visual acuity (BCVA) and side effects were evaluated retrospectively in 10 consecutive eyes (nine patients; mean age, 61.3 years) with acute CRAO treated with PGE1 monotherapy. The protocol included intravenous injection of 40 μg PGE1 twice daily (80 μg per day) for 5 days then oral PGE1 three times daily (30 μg per day) for at least 1 month. In four eyes, the retinal vessel diameters were assessed on serial fundus photographs.
The mean time to treatment was 7.1 hours (range, 1-18 hours). The mean ± SD logarithm of the minimum angle of resolution (logMAR) BCVAs at baseline and 1 month after initiation of therapy were 2.67 ± 0.54 (range, 3.00-1.70) and 0.52 ± 0.62 (range, 2.00 to -0.18), respectively (P = 0.005); the BCVA improved by 1.0 or more logMAR unit at 1 month in all eyes. The BCVA improvement was correlated negatively with the time to treatment (ρ = -0.655, P = 0.0492), but was not correlated with age (ρ = -0.473, P = 0.156) and did not differ between sexes (P = 0.0871). Compared with baseline, the mean changes in the vessel diameters in four cases were 151.1% (range, 115.1%-188.0%) in the arteries and 191.0% (range, 127.2%-246.4%) in the veins 1 day after initiation of therapy. Angialgia during injection was the only side effect.
Systemic administration of PGE1 for acute CRAO rapidly restores retinal blood flow by its vasodilatory effects, improves VA, is well tolerated with few side effects, and requires no special training.