Association of Dietary Nutrient Intake with Early Age-Related Macular Degeneration in Japanese-Americans.

Lifestyle factors may be associated with the development of age-related macular degeneration (AMD), in addition to demographic and genetic factors. The purpose of this cross-sectional study is to elucidate the association between nutrient intake and AMD in the Japanese-American population living in Los Angeles. We conducted a medical survey of Japanese immigrants and their descendants living in Los Angeles, including interviews on dietary habits, fundus photography, and physical examinations. Participants were classified into early AMD and control groups on the basis of fundus photographic findings. Consequently, among the 555 participants, 111 (20.0%) were diagnosed with early AMD. There were no late-stage AMD participants. Multivariate logistic regression analysis showed that the intake of animal fat and saturated fatty acids (SFA) was positively associated with early AMD (p for trend = 0.01 for animal fat, p for trend = 0.02 for SFA), and the intake of vegetable fat, total carbohydrate, simple carbohydrate, sugar, and fructose was inversely associated with early AMD (p for trend = 0.04 for vegetable fat, p for trend = 0.046 for carbohydrate, p for trend = 0.03 for simple carbohydrate, p for trend = 0.046 for sugar, p for trend = 0.02). Our findings suggest that excessive animal fat and SFA intake increases the risk for early AMD in Japanese-Americans whose lifestyles have been westernized.

Association between radiation, glaucoma subtype, and retinal vessel diameter in atomic bomb survivors.

We examined the relationship between glaucoma subtype and retinal vascular caliber as markers of ocular circulation. Subjects were Japanese atomic bomb survivors in Hiroshima and Nagasaki. After a screening examination, potential cases were subjected to further definitive examination. The diameters of central retinal artery and vein equivalents (CRAE and CRVE) on digitized retinal photographs were measured using an established method. Generalized linear regression analyses were used to examine the associations among vessel diameters, radiation exposure, and prevalence of glaucoma subtypes among the study subjects. We identified 196 cases of glaucoma (12%) based on optic disc appearance, perimetry results, and other ocular findings. The main subtypes were primary angle-closure glaucoma, primary open-angle glaucoma and normal-tension glaucoma (NTG). NTG was the dominant subtype (78%). NTG was negatively associated with CRAE and CRVE, and positively associated with radiation dose. CRVE was negatively associated with radiation dose and the association was unclear for CRAE. The smaller retinal vessel caliber in NTG patients than in subjects without glaucoma may indicate an association between ocular blood flow and the pathogenesis of NTG. However, significant relationships among vessel calibers, NTG and radiation exposure were not clear.

Association between glaucoma eye drops and hyperemia.

PURPOSE: We used an image analysis software program to quantitatively investigate conjunctival injection in patients treated with eye drops for glaucoma. METHODS: We compared 169 patients (89 men and 80 women) with a diagnosis of glaucoma. Photographs of the conjunctiva were taken on the temporal side of each patient's right eye using a slit lamp. We determined the mean pixel frequencies of the conjunctival blood vessels from the photographs. RESULTS: The ocular hyperemia of the patients being treated with prostaglandins was more severe than that of the patients being treated with beta-blockers or no eye drops. In multiple comparisons of each of the eye drops, the control group had a significantly lower degree of hyperemia than did the patients being treated with each of the various prostaglandin analogs (latanoprost, travoprost, tafluprost, and bimatoprost). Among the patients receiving prostaglandin, the percentage of those with hyperemia was highest in the bimatoprost users, followed in order by the travoprost, latanoprost, and tafluprost users. However, no significant differences were found among the different prostaglandin analogs in terms of the percentage of patients with hyperemia. CONCLUSION: Our software program may be useful for evaluating the hyperemic effects of eye drops used for glaucoma. The particular type of prostaglandin analog seems to determine the level of conjunctival hyperemia during ocular hypotensive medical treatment.

Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study.

PURPOSE: To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. METHODS: The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. RESULTS: Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75-1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. CONCLUSIONS: No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors.

A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.

Is the association between smoking and the retinal venular diameter reversible following smoking cessation?

PURPOSE: Wider retinal venular caliber is shown to be associated with an increased risk of stroke, and smoking is associated with a wider retinal venular caliber. However, the impact of smoking cessation on the retinal vessels has not been previously reported. We examined this issue in an adult cohort of atomic bomb survivors. METHODS: In the Adult Health Study of Japanese atomic bomb survivors, 1664 subjects had retinal photographs taken from 2006 to 2008. The central retinal artery and vein equivalents (CRAE and CRVE) were calculated using a semiautomated software program. Multiple surveys have assessed the effects of smoking since 1963. The associations between smoking, the time since cessation, and the retinal vessel caliber were determined using linear mixed effects models. RESULTS: The CRVE was associated with an increased number of cigarettes smoked per day among women after adjusting for potential confounding factors (age, sex, blood pressure, hypertensive medications, white blood cell count, diabetes, body mass index, lipids, and radiation dose). Females who smoked 10 cigarettes per day had a 6.9-µm wider mean CRVE (P = 0.001) than nonsmokers. Females who had stopped smoking for 10 or more years had a mean CRVE similar to those who had never smoked (191.8 vs. 194.4 µm; P = 0.23). These associations were not observed in males or for CRAE. CONCLUSIONS: Wider retinal venular caliber is associated with smoking in Japanese females; however, this association becomes nonsignificant after 10 or more years of smoking cessation, suggesting that the impact of smoking on retinal venular dilation is reversible following long-term smoking cessation.

Development of automated conjunctival hyperemia analysis software.

Conjunctival hyperemia is observed in a variety of ocular inflammatory conditions. The evaluation of hyperemia is indispensable for the treatment of patients with ocular inflammation. However, the major methods currently available for evaluation are based on nonquantitative and subjective methods. Therefore, we developed novel software to evaluate bulbar hyperemia quantitatively and objectively. First, we investigated whether the histamine-induced hyperemia of guinea pigs could be quantified by image analysis. Bulbar conjunctival images were taken by means of a digital camera, followed by the binarization of the images and the selection of regions of interest (ROIs) for evaluation. The ROIs were evaluated by counting the number of absolute pixel values. Pixel values peaked significantly 1 minute after histamine challenge was performed and were still increased after 5 minutes. Second, we applied the same method to antigen (ovalbumin)-induced hyperemia of sensitized guinea pigs, acquiring similar results except for the substantial upregulation in the first 5 minutes after challenge. Finally, we analyzed human bulbar hyperemia using the new software we developed especially for human usage. The new software allows the automatic calculation of pixel values once the ROIs have been selected. In our clinical trials, the percentage of blood vessel coverage of ROIs was significantly higher in the images of hyperemia caused by allergic conjunctival diseases and hyperemia induced by Bimatoprost, compared with those of healthy volunteers. We propose that this newly developed automated hyperemia analysis software will be an objective clinical tool for the evaluation of ocular hyperemia.

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.

Efficacy of amniotic membrane-assisted bleb revision for elevated intraocular pressure after filtering surgery.

PURPOSE: To compare the effectiveness of standard revision surgery using mitomycin C (MMC) with revision using amniotic membrane transplantation and MMC for elevated intraocular pressure (IOP) after trabeculectomy. PATIENTS AND METHODS: A retrospective, nonrandomized comparative study of 36 eyes of 36 patients with a failed trabeculectomy. Patients were divided into two groups, ie, a nonamnion-transplanted group and an amnion-transplanted group. The amniotic membrane was placed on the scleral flap under the conjunctiva in the amnion-transplanted group. Both groups recovered filtration of aqueous humor from the surgical site with the adjunctive use of MMC. The changes in IOP and cumulative survival rate were compared for the two groups. Success was defined as a 30% reduction in IOP from the preoperative IOP and maintenance below 21 mmHg with or without the use of antiglaucomatous agents. RESULTS: The mean preoperative IOP was not significantly different in the two groups. The mean postoperative IOP in the nonamnion group, 12.1 +/- 5.5 mmHg, was significantly lower than the IOP in the amnion group, 16.0 +/- 3.7 mmHg. Survival curves in the two groups did not reach significantly different levels. CONCLUSIONS: Conventional surgical bleb revision with MMC can significantly reduce the elevated IOP associated with a failed filtration bleb. The use of an amniotic membrane transplant did not improve the surgical outcome in our cases.