The factors associated with retinal pigment epithelium tear development in the early phase after treatment initiation for age-related macular degeneration.

PURPOSE: This study aimed to evaluate the factors associated with retinal pigment epithelium (RPE) tear development in the early phase after anti-vascular endothelial growth factor (VEGF) drug initiation in eyes with neovascular age-related macular degeneration (nAMD) and retinal pigment epithelial detachment (PED). METHODS: Treatment-naive eyes with nAMD and PED for which anti-VEGF drug injections had been initiated and followed up for at least 3 months after the 1st anti-VEGF drug injection, were retrospectively investigated. Baseline characteristics of the PEDs, including type, height, and area, were evaluated using fundus photographs, fluorescein angiography, and optical coherence tomography images. The association between patient age, sex, medical history, PED characteristics, and the development of RPE tears within 3 months of starting anti-VEGF therapy was examined. RESULTS: This study included 244 eyes (230 patients; mean age 75.0 years, 159 males and 71 females). RPE tears occurred in 13 eyes (5.3%) within 3 months of the start of anti-VEGF therapy. Multivariate analysis showed an association of the development of RPE tears with PED height (every 100 µm, odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.07-2.12, p = 0.019), PED area (every 10 mm2, OR: 3.02, CI: 1.22-7.46, p = 0.016), and the presence of fibrovascular PED (OR: 59.22, CI: 4.12-850.59, p = 0.002). Eyes with cleft (the hypo-reflective space beneath the fibrovascular PED) were more likely to develop an RPE tear (p = 0.01, χ-square test). CONCLUSIONS: Fibrovascular PED, large PED area, high PED height, and the cleft finding are independent risk factors for the development of RPE tears early after the administration of anti-VEGF drugs.

Wide-Field Choroidal Thickness Analysis after Half-Fluence Photodynamic Therapy Combined with Intravitreal Aflibercept Injection in Pachychoroid Neovasculopathy.

Background: Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Methods: Seventeen eyes with PNV that underwent half-fluence PDT with an adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9-18 mm from the fovea. The <9 and 9-18 mm subfields were divided into four quadrants. Results: Choroidal thickness in each subfield decreased significantly after half-fluence PDT (p < 0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9 mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. Conclusions: Half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

Association between corneal hysteresis and glaucoma in a Japanese population: the Hisayama Study.

AIMS: To investigate the association between corneal hysteresis and the presence of glaucoma and its subtypes in a general Japanese population. METHODS: We analysed the data of 2338 Japanese community-dwellers aged ≥40 years (1059 men, 1279 women) who underwent an eye examination in 2018 as part of the population-based, cross-sectional Hisayama Study. Participants were divided into quartile levels of corneal hysteresis, which had been measured with an ocular response analyzer. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. We conducted a logistic regression analysis to determine the ORs and their 95% CIs for the presence of outcomes according to the corneal hysteresis quartiles. RESULTS: Glaucoma was diagnosed in 154 participants: primary open-angle glaucoma (POAG), n=115; primary angle-closure glaucoma, n=17; exfoliation glaucoma, n=21 and secondary glaucoma without exfoliation glaucoma, n=1. After adjustment for confounders, the OR for prevalent glaucoma was significantly increased in the participants in the first corneal-hysteresis quartile compared with those in the fourth quartile (OR: 1.80; 95% CI: 1.03 to 3.17). Regarding glaucoma subtypes, the first-quartile participants had significantly greater likelihoods of the presence of POAG (OR: 1.63; 95% CI: 1.02 to 2.61) and exfoliation glaucoma (OR: 6.49; 95% CI: 1.44 to 29.30) compared with those in the third and fourth quartiles after adjustment for potential confounders. CONCLUSIONS: These results demonstrated a significant inverse association between corneal hysteresis and the likelihood of glaucoma, suggesting that the measurement of corneal hysteresis would provide useful information for elucidating the aetiology of glaucoma.

Differences in Central and Peripheral Choroidal Thickness among the Subtypes of Age-Related Macular Degeneration in an Asian Population.

Age-related macular degeneration (AMD) causes visual impairment in individuals who are >50 years of age. However, no study has investigated AMD when using ultra-wide-field swept-source optical coherence tomography (UWF SS-OCT). We aimed to evaluate central and peripheral choroidal thicknesses using UWF SS-OCT, and to compare these across the AMD subtypes. We included 75 eyes of patients with typical AMD (tAMD), 56 with polypoidal choroidal vasculopathy (PCV), 29 with pachychoroid neovasculopathy (PNV), and 12 with retinal angiomatous proliferation (RAP). To compare choroidal thicknesses in the central and peripheral choroids, we established subfields of <3 mm, <9 mm, and 9-18 mm from the fovea. PNV patients were significantly younger than those with tAMD (p = 0.01). The choroidal thicknesses of PNV were significantly greater than that of tAMD in all subfields (p < 0.01), and choroidal thickness significantly correlated with age and axial length in all subfields (p < 0.05). Even after adjusting for age and axial length, the choroidal thickness in PNV was significantly greater than that in tAMD (p < 0.05). In addition, the ratio of the posterior <9 mm to a peripheral 9-18 mm choroidal thickness in PNV was significantly greater than that in tAMD (p < 0.01). A thickened choroid in PNV was more pronounced in the posterior choroid than in the periphery.

Association Between Choroidal Thickness and Myopic Maculopathy in a Japanese Population: The Hisayama Study.

Purpose: To examine the association between choroidal thickness and myopic maculopathy in a general Japanese population. Design: Population-based cross-sectional study. Participants: A total of 2841 residents of a Japanese community aged ≥ 40 years, who consented to participate and had available data of choroidal thickness and fundus photographs, were enrolled in this study. Methods: The choroidal thickness was measured by swept-source OCT. Participants were divided into quartiles of choroidal thickness. Myopic maculopathy was defined according to the classification system of the Meta-analysis of Pathologic Myopia Study Group. Main outcome measures were odds ratios (ORs) of choroidal thickness for prevalent myopic maculopathy. The ORs and 95% confidence intervals (CIs) were estimated using a logistic regression model. Main Outcome Measures: Prevalent myopic maculopathy. Results: Eighty-one participants had myopic maculopathy (45 diffuse chorioretinal atrophy, 31 patchy chorioretinal atrophy, and 5 macular atrophy). Individuals in the lowest quartile of choroidal thickness had a significantly greater OR for the presence of myopic maculopathy than those in the highest quartile of choroidal thickness (OR: 4.78 [95% CI: 1.78-16.72]) after adjusting for confounders, including axial length. The sensitivity analysis among the 1176 myopic individuals with axial length of ≥ 24.0 mm also showed that thinner choroidal thickness was significantly associated with prevalent myopic maculopathy. Conclusions: The present study demonstrated the significant inverse association between choroidal thickness and the likelihood of myopic maculopathy, suggesting that the measurement of choroidal thickness in addition to axial length would be useful for assessing the risk of myopic maculopathy and elucidating its pathogenesis. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Secular trends in the prevalence, incidence, and progression of diabetic retinopathy: the Hisayama Study.

PURPOSE: To examine the secular trends in the prevalence, incidence, and progression rates of diabetic retinopathy (DR) in a Japanese community. METHODS: Community-dwelling Japanese residents aged ≥ 40 years with diabetes participated in comprehensive systemic and ophthalmological surveys, including an examination for DR, in 1998 (n = 220), 2007 (n = 511), 2012 (n = 515), and 2017 (n = 560). DR was assessed using colour fundus photographs after pupil dilation according to the modified Airlie House classification system. To compare the frequencies of newly developed or progressed DR between the studied decades, two eye cohorts were established (the 2000s cohort included 145 participants examined in 1998 and 2007; the 2010s cohort included 255 participants examined in 2007, 2012, and 2017). Trends in the prevalence, incidence, and progression rate of DR were tested by logistic regression analysis with a generalised estimating equation. RESULTS: The age-adjusted prevalence of DR among individuals with diabetes decreased significantly with time from 1998 to 2017 (27.4% in 1998, 22.8% in 2007, 12.8% in 2012, and 6.4% in 2017; p for trend < 0.001). During this period, the prevalence of DR was decreasing in every haemoglobin A1c category, but it remained constant in the high systolic blood pressure category. In addition, the rates of new-onset of DR were significantly lower in the 2010s compared to the 2000s (p < 0.001). CONCLUSION: Our findings suggest that the prevalence and incidence of DR among diabetic people significantly decreased with time over the past two decades in a general Japanese population.

Prevalence of Glaucoma and Its Systemic Risk Factors in a General Japanese Population: The Hisayama Study.

Purpose: To estimate the prevalence of glaucoma and its risk factors in a Japanese community. Methods: This study included 3405 Japanese community dwellers who were ≥40 years of age and enrolled in the Hisayama Study. This population-based, cross-sectional study was conducted from 2017 to 2018. A glaucoma screening test was performed using stereo fundus images and swept-source optical coherence tomography. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. Results: The prevalence of glaucoma was 7.6% (95% confidence interval [CI], 6.7-8.6) overall. The prevalence of primary open-angle glaucoma (POAG) was 5.8% (95% CI, 5.0-6.6); that of primary angle-closure glaucoma (PACG) was 0.7% (95% CI, 0.5-1.1); and that of exfoliation glaucoma was 1.1% (95% CI, 0.7-1.4). In addition to aging, lower estimated glomerular filtration rate (eGFR) (odds ratio [OR] = 1.15; 95% CI, 1.02-1.33), higher intraocular pressure (OR = 1.06; 95% CI, 1.01-1.12), longer axial length (OR = 1.44; 95% CI, 1.31-1.59), and thinner central corneal thickness (CCT) (OR = 1.09; 95% CI, 1.04-1.15) were significant risk factors for POAG. Diabetes (OR = 2.81; 95% CI, 1.19-6.62) was a significant risk factor for PACG, and diabetes (OR = 2.15; 95% CI, 1.03-4.47) and thinner CCT (OR = 1.14; 95% CI, 1.02-1.28) were significant risk factors for exfoliation glaucoma. Conclusions: The prevalence of glaucoma was approximately 8%, probably due to the increase in the Japanese aging population. Not only ocular factors but also lower eGFR for POAG and diabetes for PACG and exfoliation glaucoma were risk factors in a general Japanese population. Translational Relevance: Systemic factors such as eGFR and diabetes must also be considered when implementing preventive measures against glaucoma.

Association of Inner Retinal Thickness with Prevalent Dementia and Brain Atrophy in a General Older Population: The Hisayama Study.

Purpose: To assess the association of inner retinal thickness with prevalent dementia and regional brain atrophy in a general older population of Japanese. Design: Population-based, cross-sectional study. Participants: A total of 1078 residents aged 65 years or older who participated in an eye examination, a comprehensive survey of dementia, and brain magnetic resonance imaging scanning in 2017. Methods: The thicknesses of the inner retinal layers, namely, the ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL)-were measured by swept-source OCT (SS-OCT). The association of these retinal thicknesses with the risk of the presence of dementia was estimated using restricted cubic splines and logistic regression models. Regional brain volumes were estimated separately by applying 2 different methods: voxel-based morphometry (VBM) and analysis by FreeSurfer software. The associations of GC-IPL and RNFL thickness with each brain regional volume were analyzed using multiple regression analysis. Main Outcome Measure: Prevalent dementia and regional brain atrophy. Results: Among the study participants, 61 participants (5.7%) were diagnosed with dementia. The likelihood of the presence of dementia significantly increased with lower GC-IPL thickness after adjusting for potential confounders (odds ratio, 1.62 [95% confidence interval, 1.30-2.01] per 1 standard deviation decrement in the GC-IPL thickness), but no significant association was observed with RNFL thickness. In the VBM analyses with the multivariable adjustment, lower GC-IPL thickness was significantly associated with lower volume of known brain regions related to cognitive functions (i.e., the hippocampus, amygdala, entorhinal area, and parahippocampal gyrus) and visual functions (i.e., the cuneus, lingual gyrus, and thalamus). Meanwhile, the volume of the thalamus significantly decreased with lower RNFL thickness, but none of the brain regions related to cognitive function exhibited a volume change in association with RNFL thickness. The sensitivity analysis using FreeSurfer analysis also showed that lower GC-IPL thickness was significantly associated with lower regional brain volume/intracranial volume of the hippocampus, amygdala, cuneus, lingual gyrus, and thalamus. Conclusions: Our findings suggest that the measurement of GC-IPL thickness by SS-OCT, which is a noninvasive, convenient, and reproducible method, might be useful for identifying high-risk individuals with dementia.

Characteristics of retinal pigment epithelium elevations preceding exudative age-related macular degeneration in Japanese.

INTRODUCTION: Drusen and pigmentary abnormality are found as the hallmark to predict progression of age-related macular degeneration (AMD). In Asian populations, exudative AMD often appears in the absence of drusen but are rather accompanied by pigmentary abnormality. Recently, shallow irregular retinal-pigment-epithelium (RPE) elevations (SIRE) has been shown as a sign of subclinical non-exudative macular neovascularization. In this study, we aimed to investigate the characteristics of optical coherence tomography (OCT) findings including SIRE before the appearance of exudative AMD. METHODS: We retrospective reviewed 32 cases of exudative AMD that occurred in the fellow eye within the 5-years-observation period. Color fundus photography, OCT, and fluorescein/indocyanine green angiography at the beginning of observation and at the time when exudative AMD appeared were examined to diagnose SIRE and the subtype of exudative AMD. RESULTS: Exudative AMD were found in 19 eyes with large drusen and 13 eyes without large drusen. Mean sub-foveal choroidal thickness without large drusen were significantly thicker than those with large drusen (336 ± 109 and 220 ± 96 µm, respectively; mean± SD). Six eyes with pachychoroid neovasculopathy, 4 eyes with Type 1 macular neovascularization, and 3 eyes with PCV had occurred in the fellow eye without large drusen. Among those, 6 eyes had been accompanied by SIRE with a greatest transverse linear dimension of 1 mm or more at the beginning of observation-period. Besides, small RPE elevations with a longest diameter of less than 1 mm had been observed in other 5 eyes. Three cases of polypoidal choroidal vasculopathy had originated from small RPE elevations. Moreover, pachyvessels, choriocapillaris thinning, or choroidal hyperpermeability were observed with SIRE or small RPE elevation. CONCLUSIONS: There is a non-drusen type of exudative AMD that originates from small RPE elevations as well as SIRE.

Cohort Profile: The Ganka-Ekigaku Network (GEN), a Network of Japanese Ophthalmological Epidemiology Studies.

PURPOSE: Japan has been known as a super-aged society, and ageing is a well-known risk factor for blinding eye diseases. However, epidemiological studies in ophthalmology are still scarce in Japan, and the sizes of the cohorts are relatively small. "Ganka-Ekigaku Network" (GEN, an acronym for the epidemiological network in ophthalmology in Japanese) is established to develop a capacity to boost each epidemiological study and enrich a potential inter-study collaboration to identify risk factors of visual impairment in aged society. METHODS: We reviewed cohort studies in Japan with the inclusion criteria as: (1) at least n = 1000 at baseline, (2) multiple modalities of ophthalmic data, and (3) diagnosis reviewed by ophthalmologist(s), and (4) ophthalmologists are involved in the investigators group. As of January 2020, GEN includes 4 individual Japanese epidemiological studies namely, Hisayama study, Yamagata Study (Funagata), Tsuruoka Metabolomics Cohort study, and the Nagahama Prospective Genome Cohort for Comprehensive Human Bioscience. RESULTS: GEN includes approximately 25,000 Japanese participants. The baseline surveys started from 1998 to 2012, and since then the data has been prospectively collected approximately every 5 years. A variety of ophthalmic measurements and other factors have been collected in each study in GEN: ophthalmic measurements (fundus photography, optical coherence tomography, etc.), systemic conditions (laboratory data, etc.), and others (DNA, etc.). CONCLUSION: GEN is an open platform for observational ophthalmic epidemiological studies to share standardized methodologies. While each study in GEN pursues specific and original research questions, standardization of the methods will enable us to conduct reliable meta-analysis/pooled data analyses.

Five-Year Incidence of Myopic Maculopathy in a General Japanese Population: The Hisayama Study.

Importance: Myopic maculopathy is a leading cause of irreversible visual impairment worldwide. Moreover, the burden of myopic maculopathy has been expected to increase owing to the rising prevalence of myopia globally. However, there is limited epidemiologic evidence regarding the incidence of and risk factors for myopic maculopathy. This study from Japan, with a relatively high prevalence of myopia, could provide valuable information related to these issues. Objective: To estimate the incidence of myopic maculopathy and its risk factors in Hisayama in southwestern Japan. Design, Setting, and Participants: A population-based prospective cohort study in a Japanese community in Hisayama, Japan. The study included a total of 2164 residents 40 years or older who had no myopic maculopathy at the baseline eye examination in 2012 and underwent follow-up eye examinations in 2017. Main Outcomes and Measures: Incidence of myopic maculopathy. The grades of myopic maculopathy were categorized based on the criteria of the Meta-analysis of Pathologic Myopia Study Group classification system. Results: The mean (SD) age of the study participants was 62.4 (10.9) years, and the proportion of men was 42.5% (920 participants). In the follow-up examination in 2017, 24 patients developed myopic maculopathy. The 5-year cumulative incidence of myopic maculopathy was 1.1% (95% CI, 0.6-1.5) overall, 1.4% (95% CI, 0.6-2.2) for men, and 0.9% (95% CI, 0.4-1.4) for women. Multiple logistic regression analysis showed that older age (per 1 year; odds ratio [OR], 1.06; 95% CI, 1.01-1.11) and longer axial length (per 1 mm; OR, 2.94; 95% CI, 2.19-3.95) were associated with incident myopic maculopathy. Conclusions and Relevance: Twenty-four study participants (1%) developed myopic maculopathy during the 5-year study period, which is much higher than the rate in a previous study on a Chinese population. We also confirmed that aging and longer axial length were independent and significant risk factors for myopic maculopathy. These findings should be reviewed among various populations in other parts of the world.

Long-term regular exercise and intraocular pressure: the Hisayama Study.

PURPOSE: To investigate the association between long-term regular exercise (exercise frequency and exercise time) and 5-year changes in intraocular pressure in a general Japanese population. METHODS: This population-based, cohort study was conducted in 2007. A total of 3119 Japanese community dwellers aged ≥ 40 years underwent eye examinations including intraocular pressure measurement with a noncontact tonometer. Of these, 1871 subjects (801 men and 1070 women) who underwent intraocular pressure measurement in 2012 participated. We assessed the associations of exercise frequency and exercise time with intraocular pressure using a linear regression model, adjusted for age and possible risk factors that can affect intraocular pressure. RESULTS: The mean 5-year intraocular pressure change ± standard deviation was - 0.84 ± 1.9 mmHg. After adjustment for age, sex, systolic blood pressure, diabetes, total cholesterol, high-density lipoprotein cholesterol, body mass index, waist circumference, smoking habit, alcohol intake, work intensity levels, and intraocular pressure at baseline, we observed that increased exercise frequency (times/week) and increased exercise time (min/week) were both significantly associated with reduced intraocular pressure (p < 0.05 each). In the subgroup analyses based on the presence/absence of possible confounding risk factors, there was no evidence of heterogeneity among all subgroups (p for heterogeneity > 0.2). CONCLUSIONS: Increased exercise frequency levels and increased exercise time are both independently associated with reduced intraocular pressure levels after adjustment for confounding factors.

Trends in the Prevalence of Myopia and Myopic Maculopathy in a Japanese Population: The Hisayama Study.

Purpose: To examine trends in the prevalence of myopia and myopic maculopathy in a general Japanese population. Methods: Residents of a Japanese community aged 40 years and older participated in surveys conducted in 2005, 2012, and 2017. Each participant underwent comprehensive eye examinations that included measurements of refractive error, axial lengths, and color fundus photography. Myopic maculopathy was defined according to the criteria of the Meta-analysis of Pathologic Myopia Study Group classification system. Trends in the prevalence of myopia and myopic maculopathy were tested by using a logistic regression analysis fitted by generalized estimating equations to account for individuals submitting to repeated examination. Results: The age-adjusted frequencies of myopia increased significantly from 2005 to 2017 (myopia, 37.7%-45.8%; high myopia 5.8%-9.5%; all P for trend <0.001). The age-adjusted frequency of an axial length level of 26.5 mm or more increased significantly from 2005 to 2017 (3.6%-6.0%; P for trend <0.001). The age-adjusted prevalence of myopic maculopathy also increased significantly with time (1.6% in 2005, 3.0% in 2012 and 3.6% in 2017; P for trend <0.001). Upward trends were observed in the prevalence of diffuse chorioretinal atrophy and patchy chorioretinal atrophy (all P for trend <0.05). Conclusions: Our findings suggest that the prevalence of myopia and myopic maculopathy, especially diffuse chorioretinal atrophy and patchy chorioretinal atrophy, increased significantly over the past 12 years in a general Japanese population.

Association between Axial Length and Myopic Maculopathy: The Hisayama Study.

PURPOSE: To assess the association between axial length (AL) and the prevalence of myopic maculopathy in a general Japanese population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A total of 2790 Hisayama residents 40 years of age or older who consented to participate and had available data of AL and fundus photographs for the right eyes were enrolled in this study. METHODS: Myopic maculopathy was defined as the presence of diffuse chorioretinal atrophy, patchy chorioretinal atrophy, or macular degeneration. The optimal cutoff values of axial length for identifying myopic maculopathy were estimated from the receiver operating characteristic curve. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a logistic regression analysis. MAIN OUTCOME MEASURES: Odds ratios of AL for prevalent myopic maculopathy and the optimal cutoff values of AL for detecting myopic maculopathy. RESULTS: Longer AL was associated significantly with prevalence of myopic maculopathy in both genders. The optimal cutoff values of AL for identifying myopic maculopathy were 25.9 mm in men and 25.3 mm in women. Participants with ALs of these values or longer showed a significantly higher OR for myopic maculopathy than those with AL of less than these values (men: OR, 21.23; 95% CI, 8.74-51.57; women: OR, 38.49; 95% CI, 18.03-86.49). CONCLUSIONS: The present study found that there was a positive association between AL and the likelihood of myopic maculopathy, and the cutoff levels of AL for identifying myopic maculopathy were 25.9 mm in men and 25.3 mm in women. Our findings suggest that patients with AL close to or longer than these values should undergo intensive treatment and detailed ophthalmic follow-up.

Glucose Tolerance Levels and Circumpapillary Retinal Nerve Fiber Layer Thickness in a General Japanese Population: The Hisayama Study.

PURPOSE: To investigate the relationship between glucose tolerance levels and the circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in a general Japanese population. DESIGN: Population-based, cross-sectional study. METHODS: In 2012 and 2013, a total of 2809 Japanese community dwellers aged 40-79 years in the Hisayama Study underwent eye examinations including cpRNFLT measurement with spectral domain optical coherence tomography. Of these, 1324 subjects (578 men and 746 women) were enrolled. Glucose tolerance levels were determined by a 75-g oral glucose tolerance test. We conducted an analysis of covariance to estimate the mean values of cpRNFLT according to the subjects' glucose intolerance status. RESULTS: The subjects with prediabetes or with diabetes mellitus had significantly lower age- and sex-adjusted mean cpRNFLT values than those with normal glucose tolerance (P = .04 and P = .0004, respectively). The age- and sex-adjusted mean values of cpRNFLT decreased significantly with elevating fasting plasma glucose and 2-hour postload glucose levels (all P for trend < .05). These associations were substantially unchanged after adjustment for potential confounding factors. The coexistence of poorer glucose tolerance and higher intraocular pressure levels was additively associated with thinner cpRNFLT. CONCLUSIONS: Our analyses revealed that poorer glucose tolerance was significantly associated with the reduction of cpRNFLT in a Japanese general population, suggesting that the loss of neural tissue in the eye begins at the prediabetic stage, and that hyperglycemia may play a role in the reduction of cpRNFLT.

Prevalence and Risk Factors for Polypoidal Choroidal Vasculopathy in a General Japanese Population: The Hisayama Study.

PURPOSE: To estimate the prevalence and risk factors for polypoidal choroidal vasculopathy (PCV) in a general Japanese population. METHODS: This population-based, cross-sectional study was conducted in 2007 with subjects from the Hisayama Study. Of the 3,648 residents in Hisayama, Japan, 2,663 who were ≥ 50 years old were enrolled in this study. The characteristics of PCV were determined by fundus examination or based on indocyanine green and fluorescein angiographic findings. We evaluated the contributions of the risk factors for PCV. RESULTS: Among the 207 participants with age-related macular degeneration (AMD), 174 (6.5%) had early AMD, and 33 (1.2%) had late AMD, including 10 participants with PCV (0.4%). Male and smoking habit were significant risk factors for the development of PCV. CONCLUSIONS: The prevalence of PCV is higher among Japanese subjects than Caucasians in Western countries. Male gender and smoking habit were significant risk factors for PCV in a general Japanese population.

Cataracts after Low-Dose Radiotherapy for Lymphoproliferative Disease of the Ocular Adnexa.

PURPOSE: To investigate the interval between low-dose radiotherapy and radiation-induced cataracts, and the factors affecting this interval, in patients with lymphoproliferative disease of the ocular adnexa. METHODS: A retrospective case series of 73 eyes of 59 patients who underwent radiotherapy from 1996 to 2005 with total doses ranging from 24 to 30 Gy was conducted. We investigated the relationships between the radiation-associated cataract formation intervals and age, gender, diabetes, and the use of corticosteroids. RESULTS: The mean interval was 36 months. None of the patients with lens shield developed cataracts. Age was inversely and significantly and gender was not significantly associated with the interval from first radiotherapy to cataract occurrence. The intervals did not differ significantly according to the presence of diabetes and corticosteroid therapy. CONCLUSIONS: The mean interval from the start of radiation therapy to radiation-related cataract formation was 36 months and age was a significant factor affecting this interval.

Foveal and Macular Thickness in a Japanese Population: The Hisayama Study.

PURPOSE: To examine factors associated with foveal thickness (FT) and macular thickness (MT) in Japanese persons from Hisayama. METHODS: A total of 2216 healthy eyes of 1384 participants were analyzed. Each participant underwent comprehensive physical and ophthalmic examinations, the latter including optical coherence tomography (OCT). Multiple regression analysis was used to determine the relationship of various factors (race, age, sex, refractive error, axial length, diabetes mellitus, fasting plasma glucose levels, alcohol intake and smoking status) to FT (central 1-mm foveal area) and MT (central 3-mm foveal region). RESULTS: Results of multiple linear regression analysis indicated that age was positively associated with FT (ß coefficient 0.214 µm). FT was significantly smaller in women than men (ß coefficient -9.146 µm). For both sexes, body height was positively correlated (ß coefficient 0.257 µm), while refractive error and current smoking were negatively associated (ß coefficients -1910 µm and -4.410 µm, respectively) with FT. With respect to MT, there were negative associations between age, sex (female), and refractive error (ß coefficients -0.268 µm, -4.815 µm and -0.699 µm, respectively). For both sexes, body height was positively correlated (ß coefficient 0.227 µm), while hypertension and current smoking were negatively associated (ß coefficients -1.999 µm and -2.758 µm, respectively) with MT. CONCLUSIONS: Our results indicated that age, body height, refractive error, and current smoking were significantly associated with FT, whereas age, body height, refractive error, current smoking, and hypertension were significantly related to MT. Women had significantly smaller FT and MT than men.

Insulin Resistance Is a Risk Factor for Increased Intraocular Pressure: The Hisayama Study.

PURPOSE: To investigate association of the homeostasis model assessment of insulin resistance (HOMA-IR), a surrogate index of insulin resistance, with IOP in a general Japanese population. METHODS: In 2007, a total of 3119 Japanese community-dwellers, aged 40 years or older, underwent eye examinations, including IOP measurement with a noncontact tonometer. Of these, 2254 residents participated in this study. Fasting serum glucose and plasma insulin were measured to determine the HOMA-IR. The association of HOMA-IR with IOP was assessed using a linear regression model, adjusted for age and possible risk factors that can elevate IOP. RESULTS: The mean IOP ± SD was 13.7 ± 2.7 mm Hg in the right eye and 13.6 ± 2.7 mm Hg in the left eye. After adjusting for age, sex, systolic blood pressure, diabetes, total cholesterol, high-density lipoprotein cholesterol, body mass index, waist circumference, smoking habits, alcohol intake, and regular exercise, increased HOMA-IR levels were significantly associated with increasing IOP (P < 0.05). In the subgroup analyses based on the presence or absence of possible confounding risk factors, there was no evidence of heterogeneity between all subgroups (P for heterogeneity > 0.08). CONCLUSIONS: The HOMA-IR is independently associated with elevated IOP levels after adjustment for confounding factors.

Prevalence and risk factors for myopic retinopathy in a Japanese population: the Hisayama Study.

PURPOSE: To examine the prevalence of myopic retinopathy and its risk factors in a general Japanese population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: In 2005, a total of 1969 Hisayama residents aged ≥ 40 years consented to participate in this study. Of these, 1892 subjects with adequate data were enrolled. METHODS: Each participant underwent comprehensive physical and eye examinations that included measurements of refractive error, axial lengths, and color fundus photography. Myopic retinopathy was defined as the presence of diffuse chorioretinal atrophy, patchy chorioretinal atrophy, lacquer cracks, or macular atrophy. MAIN OUTCOME MEASURES: Prevalence of myopic retinopathy. RESULTS: Thirty-three participants had myopic retinopathy and the prevalence was 1.7% (2.2% in women and 1.2% in men). The prevalence of myopic retinopathy increased significantly with advancing age. Diffuse chorioretinal atrophy, patchy chorioretinal atrophy, lacquer cracks, and macular atrophy were present in 1.7%, 0.4%, 0.2%, and 0.4% of subjects, respectively. In multivariate analysis, myopic retinopathy was significantly associated with older age (per 1 year: odds ratio [OR], 1.12; 95% confidence interval [CI], 1.07-1.18), female gender (OR, 3.29; 95% CI, 1.09-9.92), and longer axial length (per 1 mm: OR, 4.20; 95% CI, 3.03-5.83). CONCLUSIONS: The prevalence of myopic retinopathy was 1.7% in a general Japanese population. Older age, female gender, and longer axial length were significant risk factors for myopic retinopathy.