Ophthalmology (Eye & Ear Hospital) - Research Publications

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    A genome-wide association study of corneal astigmatism: The CREAM Consortium
    Shah, RL ; Li, Q ; Zhao, W ; Tedja, MS ; Tideman, JWL ; Khawaja, AP ; Fan, Q ; Yazar, S ; Williams, KM ; Verhoeven, VJM ; Xie, J ; Wang, YX ; Hess, M ; Nickels, S ; Lackner, KJ ; Parssinen, O ; Wedenoja, J ; Biino, G ; Concas, MP ; Uitterlinden, A ; Rivadeneira, F ; Jaddoe, VWV ; Hysi, PG ; Sim, X ; Tan, N ; Tham, Y-C ; Sensaki, S ; Hofman, A ; Vingerling, JR ; Jonas, JB ; Mitchell, P ; Hammond, CJ ; Hoehn, R ; Baird, PN ; Wong, T-Y ; Cheng, C-Y ; Teo, YY ; Mackey, DA ; Williams, C ; Saw, S-M ; Klaver, CCW ; Guggenheim, JA ; Bailey-Wilson, JE (MOLECULAR VISION, 2018-02-05)
    PURPOSE: To identify genes and genetic markers associated with corneal astigmatism. METHODS: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. RESULTS: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). CONCLUSIONS: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.
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    Potential Utility of Retinal Imaging for Alzheimer's Disease: A Review
    Liao, H ; Zhu, Z ; Peng, Y (FRONTIERS MEDIA SA, 2018-06-22)
    The ensuing upward shift in demographic distribution due to the increase in life expectancy has resulted in a rising prevalence of Alzheimer's disease (AD). The heavy public burden of AD, along with the urgent to prevent and treat the disease before the irreversible damage to the brain, calls for a sensitive and specific screening technology to identify high-risk individuals before cognitive symptoms arise. Even though current modalities, such as positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarker, showed their potential clinical uses in early detection of AD, the high cost, narrow isotope availability of PET probes and invasive characteristics of CSF biomarker limited their broad utility. Therefore, additional tools for detection of AD are needed. As a projection of the central nervous system (CNS), the retina has been described as a "window to the brain" and a novel marker for AD. Low cost, easy accessibility and non-invasive features make retina tests suitable for large-scale population screening and investigations of preclinical AD. Furthermore, a number of novel approaches in retina imaging, such as optical coherence tomography (OCT), have been developed and made it possible to visualize changes in the retina at a very fine resolution. In this review, we outline the background for AD to accelerate the adoption of retina imaging for the diagnosis and management of AD in clinical practice. Then, we focus on recent findings on the application of retina imaging to investigate AD and provide suggestions for future research directions.
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    Cognitive Performance Concomitant With Vision Acuity Predicts 13-Year Risk for Mortality
    Liao, H ; Zhu, Z ; Wang, H ; Rong, X ; Young, CA ; Peng, Y (FRONTIERS MEDIA SA, 2019-03-22)
    Objective: To assess the joint impact of cognitive performance and visual acuity on mortality over 13-year follow-up in a representative US sample. Methods: Data from National Health and Nutrition Examination Survey (NHANES) participants (≥18 years old) were linked with the death record data of the National Death Index (NDI) with mortality follow-up through December 31, 2011. Cognitive performance was evaluated by the Digit Symbol Substitution Test (DSST) and cognitive performance impairment was defined as the DSST score equal to or less than the median value in the study population. Visual impairment (VI) was defined as presenting visual acuity worse than 20/40 in the better-seeing eye. Risks of all-cause and specific-cause mortality were estimated with Cox proportional hazards models after adjusting for confounders. Results: A total of 2,550 participants 60 years and older from two waves of (NHANES, 1999-2000, 2001-2002) were included in the current analysis. Over a median follow-up period of 9.92 years, 952 (35.2%) died of all causes, of whom 239 (23.1%), 224 (24.0%), and 489 (52.9%) died from cardiovascular disease (CVD), cancer, and non-CVD/non-cancer mortality, respectively. Cognitive performance impairment and VI increased the odds for mortality. Co-presence of VI among cognitive impaired elderly persons predicted nearly a threefold increased risk of all-cause mortality [hazard ratios (HRs), 2.74; 95% confidence interval (CI), 2.02-3.70; P < 0.001) and almost a fourfold higher risk of non-CVD/non-cancer mortality (HR, 3.72; 95% CI, 2.30-6.00; P < 0.001) compared to having neither impairment. Conclusion: People aged 60 years and over with poorer cognitive performance were at higher risk of long-term mortality, and were especially vulnerable to further mortality when concomitant with VI. It is informative for clinical implication in terms of early preventive interventions.
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    Hyponatremia is a potential predictor of progression in radiation-induced brain necrosis: a retrospective study
    Liao, H ; Zhu, Z ; Rong, X ; Wang, H ; Peng, Y (BMC, 2018-08-29)
    BACKGROUND: To investigate the prognostic value of hyponatremia, defined as serum sodium level < 135 mEq/L, in radiation-induced brain necrosis (RN) patients. METHODS: We performed a retrospective analysis of the RN patients (The patients included in our study had a history of primary cancers including nasopharyngeal carcinoma/glioma/oral cancer and received radiotherapy previously and then were diagnosed with RN) treated in Sun yat-sen Memorial Hospital from January 2013 to August 2015. Patients without cranial magnetic resonance imaging (MRI) scan and serum sodium data were excluded. Progression was identified when the increase of edema area ≥ 25% on the MRI taken in six months comparing with those taken at the baseline. Factors that might associate with prognosis of RN were collected. Multivariable logistic regression analyses were used to identify potential predictors. RESULTS: We total included 135 patients, 32 (23.7%) of them with hyponatremia and 36 (26.7%) with RN progression. Percentage of progression was roughly three fold in hyponatremia patients compared with nonhyponatremia patients (53.1% versus 18.4%), translating into a 5-fold increased odds ratio (P <  0.001). Multivariable analyses identified hyponatremia as a potential predictor of progression (OR, 4.82; 95% CI [1.94-11.94]; P = 0.001). CONCLUSIONS: Hyponatremia was identified as a potential predictor for the progression of patients with RN. Hyponatremia management in patients with RN should be paid much more concern in clinical practice.
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    Aldose Reductase Gene Polymorphism and Diabetic Retinopathy Susceptibility
    Abhary, S ; Burdon, KP ; Laurie, KJ ; Thorpe, S ; Landers, J ; Goold, L ; Lake, S ; Petrovsky, N ; Craig, JE (AMER DIABETES ASSOC, 2010-08)
    OBJECTIVE: Aldose reductase (ALR) is involved in diabetic microvascular damage via the polyol pathway. A recent meta-analysis found genetic variation in the ALR gene (AKR1B1) to be significantly associated with diabetic retinopathy (DR). We investigated the genetic association of AKR1B1 with DR. RESEARCH DESIGN AND METHODS: The study enrolled 909 individuals with diabetes. Participants were genotyped for an AKR1B1 (CA)n microsatellite and 14 tag single nucleotide polymorphisms, and ophthalmological assessment was performed. RESULTS: A total of 514 individuals were found to have DR. rs9640883 was significantly associated with DR (P = 0.0005). However, AKR1B1 variation was not independently associated with DR development after adjusting for relevant clinical parameters. rs9640883 was associated with duration of diabetes (P = 0.002). CONCLUSION: Many previous reports have failed to account for known risk factors for DR. The commonly reported association of AKR1B1 with DR may be due to an association of the gene with younger age at onset of diabetes.
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    Alterations in Retinal Microvascular Geometry in Young Type 1 Diabetes
    Sasongko, MB ; Wang, JJ ; Donaghue, KC ; Cheung, N ; Benitez-Aguirre, P ; Jenkins, A ; Hsu, W ; Lee, M-L ; Wong, TY (AMER DIABETES ASSOC, 2010-06)
    OBJECTIVE: To describe retinal microvascular geometric parameters in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes (aged 12-20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed. RESULTS: Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P 8.5 vs.
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    Correlation Between Macular Integrity Assessment and Optical Coherence Tomography Imaging of Ellipsoid Zone in Macular Telangiectasia Type 2
    Mukherjee, D ; Lad, EM ; Vann, RR ; Jaffe, SJ ; Clemons, TE ; Friedlander, M ; Chew, EY ; Jaffe, GJ ; Farsiu, S ; Sahel, J-A ; Guymer, R ; Soubrane, G ; Gaudric, A ; Schwartz, S ; Constable, I ; Cooney, M ; Egan, C ; Singerman, L ; Gillies, MC ; Friedlander, M ; Pauleikhoff, D ; Moisseiev, J ; Rosen, R ; Murphy, R ; Holz, F ; Comer, G ; Blodi, B ; Do, D ; Brucker, A ; Narayanan, R ; Wolf, S ; Rosenfeld, P ; Bernstein, PS ; Miller, JW (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017-05)
    PURPOSE: To correlate ellipsoid zone (EZ) defects on spectral-domain optical coherence tomography (SD-OCT) with retinal sensitivity loss on macular integrity assessment (MAIA) microperimetry in macular telangiectasia type 2 (MacTel). METHODS: Macular SD-OCT volumes and microperimetry maps were obtained during the international, multicenter, randomized phase 2 trial of ciliary neurotrophic factor for type 2 MacTel on two visits within 5 days of one another. Software was developed to register SD-OCT to MAIA scanning laser ophthalmoscopy images and to overlay EZ defect areas on the microperimetry maps generated from microperimetry sensitivity values at specific points and from interpolated sensitivity values. A total of 134 eyes of 67 patients were investigated. RESULTS: The semiautomated registration algorithm was found to be accurate, both qualitatively by visual inspection of the nearly perfect overlap of the retinal vessels and quantitatively as assessed by interobserver reliability metrics performed in 98 eyes of 49 patients (intraclass correlation of aggregate retinal sensitivity loss >0.99). Aggregate retinal sensitivity loss within the EZ defect area was highly correlated with EZ defect area (Pearson correlation coefficient 0.93 and 0.92 at screening and baseline for noninterpolated maps; both were 0.94 for interpolated maps; P values <0.001). CONCLUSIONS: With our software and image processing algorithms, there is nearly perfect correlation between retinal sensitivity on microperimetry and EZ defect area on SD-OCT. Our software allows determination of functional and structural changes with increasing disease severity and demonstrates that functional loss on microperimetry may be used as a surrogate marker of EZ loss on SD-OCT in type 2 MacTel.
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    One-year outcome of intravitreal aflibercept injection for age-related macular degeneration resistant to ranibizumab: rapid morphologic recovery and subsequent visual improvement.
    Hirakata, T ; Fujinami, K ; Watanabe, K ; Sasaki, M ; Noda, T ; Akiyama, K (Informa UK Limited, 2016)
    OBJECTIVE: To describe the 1-year efficacy of aflibercept in Japanese patients with age-related macular degeneration (AMD) who were resistant to ranibizumab treatment. DESIGN: Retrospective case series. PARTICIPANTS: Fourteen consecutive eyes of 14 patients with AMD were enrolled who had no substantial response or developed resistance to intravitreal ranibizumab injections. METHODS: All patients were subcategorized into one of two subtypes of AMD: seven patients with occult choroidal neovascularization (CNV) and seven with polypoidal choroidal vasculopathy (PCV). Serial intravitreal aflibercept (IVA) injections were administered. Comprehensive ophthalmic examinations, including optical coherence tomography, were conducted at baseline and at follow-up examinations at 1, 3, 6, and 12 months after the initial IVA injection. The best-corrected visual acuity converted to logarithm of the minimum angle of resolution (logMAR) and central macular thickness (CMT) at each follow-up visit were compared with the baseline values. The anatomic response was also assessed with absorption or reduction of fluid in the subretina or subretinal pigment epithelial space. RESULTS: The logMAR best-corrected visual acuity improved significantly at 3, 6, and 12 months in the total cohort: at 3 and 6 months in patients with occult CNV and at 3 and 12 months in patients with PCV. The CMT decreased significantly at all follow-up visits in the total cohort as well as in both subtypes, except for the CMT at 6 months in PCV patients. The anatomic improvement was also demonstrated in all cases, and pigment epithelial detachments tended to be resolved more rapidly in patients with PCV than in patients with occult CNV. CONCLUSION: Conversion to IVA was effective in patients with AMD resistant to ranibizumab, showing rapid morphologic improvement. The logMAR visual acuity was raised significantly within 12 months, and the clinical course of visual acuity improvement may differ according to the AMD subtypes.
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    Advanced quantitative analysis of the sub-retinal pigment epithelial space in recurrent neovascular age-related macular degeneration
    Sasaki, M ; Kato, Y ; Fujinami, K ; Hirakata, T ; Tsunoda, K ; Watanabe, K ; Akiyama, K ; Noda, T ; Clark, SJ (PUBLIC LIBRARY SCIENCE, 2017-11-02)
    To quantitatively evaluate changes in the sub-retinal pigment epithelial (RPE) space and determine the association with recurrent neovascular age-related macular degeneration (AMD). Twenty-two eyes treated with intravitreal aflibercept for treatment-naïve neovascular AMD were studied retrospectively. The sub-RPE area, volume, and central retinal thickness (CRT) were evaluated 1 and 2 months after the loading phase using spectral-domain optical coherence tomography. Recurrence was defined as newly detected neovascular activity during the 6 months after the loading phase. In eyes with recurrent AMD, the sub-RPE area increased significantly (P = 0.036) from 1 to 2 months after the loading phase and the sub-RPE volume increased marginally (P = 0.06). Subgroup analysis showed significant (P = 0.008 and P = 0.016, respectively) increases in the sub-RPE area and volume in typical AMD. In eyes with no recurrence, no significant changes occurred in the two parameters. No significant CRT changes occurred in eyes with or without a recurrence. A quantitative analysis demonstrated an increased likelihood of the sub-RPE space shortly after the loading phase in eyes with recurrent AMD; no changes occurred in eyes without a recurrence. These early changes in the sub-RPE space could indicate disease activity and are valuable for predicting recurrences of neovascular AMD.
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    High Myopia and Its Associated Factors in JPHC-NEXT Eye Study: A Cross-Sectional Observational Study.
    Mori, K ; Kurihara, T ; Uchino, M ; Torii, H ; Kawashima, M ; Sasaki, M ; Ozawa, Y ; Yamagishi, K ; Iso, H ; Sawada, N ; Tsugane, S ; Yuki, K ; Tsubota, K (MDPI AG, 2019-10-25)
    The increasing prevalence of high myopia has been noted. We investigated the epidemiological characteristics and the related factors of high myopia in a Japanese adult population. Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) Eye Study was performed in Chikusei-city, a rural area in mid-east Japan, between 2013 and 2015. A cross-sectional observational analysis was conducted to investigate prevalence and related factors of high myopia. A total of 6101 participants aged ≥40 years without a history of ocular surgeries was included. High myopia was defined as a spherical equivalent refraction of ≤-6.00 diopters according to the American Academy of Ophthalmology. Potential high myopia-related factors included intraocular pressure (IOP), corneal structure, corneal endothelial cell density, age, height, body mass index, heart rate, blood pressure, biochemical profile, and current history of systemic and ocular disorders. The odds ratios of high myopia were estimated using the logistic regression models adjusted for the associated factors. The prevalence of high myopia was 3.8% in males and 5.9% in females with a significant difference. Age was inversely associated, IOP was positively associated, and none of other factors were associated with high myopia in both sexes. In conclusion, only age and IOP were associated with high myopia in this community-based sample.