Associations Between Methylenetetrahydrofolate Reductase Polymorphisms, Serum Homocysteine Levels, and Incident Cortical Cataract.

IMPORTANCE: Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been shown to influence homocysteine levels; homocysteine has been implicated as a cataractogenic stressor. OBJECTIVE: To investigate the associations of MTHFR polymorphisms and serum homocysteine levels with incident cortical cataract in an older population. DESIGN, SETTING, AND PARTICIPANTS: From 1992 to 1994, a population-based cohort study, the Blue Mountains Eye Study, was conducted with 3654 residents (82.4% of eligible participants) of the Blue Mountains region aged 49 years and older. At the second (1997-1999, 5-year follow-up) and third (2002-2004, 10-year follow-up) surveys, 2334 (75.8% of survivors) and 1952 (76.7% of survivors) were examined, respectively. For this report, the second survey serves as baseline when homocysteine levels were assessed, and 5-year incidence of cataract refers to incidence estimated from the second to the third survey. After excluding participants with no follow-up data or DNA or who had previous cortical cataract or cataract surgery, 757 participants were included in gene and environment analyses. This current project on associations with cataract was designed initially March 19, 2013, and completed April 14, 2014. Cataract was assessed using the Wisconsin Cataract Grading system. Two MTHFR polymorphisms, C677T (rs1801133) and A1298C (rs1801131), were included. Serum homocysteine levels were assessed following standard methods. MAIN OUTCOMES AND MEASURES: Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals for incident cortical cataract, after adjusting for age, sex, smoking status, hypertension, diabetes, education, and myopia. Path analysis was performed to explore a possible pathway of MTHFR polymorphisms via homocysteine levels to cortical cataract. RESULTS: The mean (SD) age of the 1726 participants in the Blue Mountains Eye Study 2 cohort with normal homocysteine levels was 68.3 (8.1) years and 73.2 (8.5) years for those with elevated homocysteine levels. Both the C677T polymorphism (CT/TT vs CC: OR = 1.50; 95% CI = 1.01-2.23) and elevated homocysteine levels (>15 µmol/L: OR = 2.24; 95% CI = 1.38-3.63) were independently associated with increased risk of cortical cataract. Path analysis showed that the genetic effect on cortical cataract was partially mediated via homocysteine levels. Combined CT/TT genotypes and elevated homocysteine levels were associated with a 3-fold risk of cortical cataract (OR = 3.74; 95% CI = 1.79-7.80). The synergy index of both exposures was 1.34 (95% CI = 0.44-4.01). CONCLUSIONS AND RELEVANCE: MTHFR polymorphism and elevated homocysteine levels contributed separately and jointly to increased risk of cortical cataract. If these findings are confirmed, homocysteine levels may be a therapeutic target to reduce risk of cortical cataract in persons carrying genetic risk.

Association of open-angle glaucoma loci with incident glaucoma in the Blue Mountains Eye Study.

PURPOSE: To determine if open-angle glaucoma (OAG)-associated single nucleotide polymorphisms (SNPs) are associated with incident glaucoma and if such genetic information is useful in OAG risk prediction. DESIGN: Case-control from within a population-based longitudinal study. METHODS: study population: Individuals aged over 49 years of age living in the Blue Mountains region west of Sydney and enrolled in the Blue Mountains Eye Study. observation: Cases for this sub-study (n = 67) developed incident OAG between baseline and 10-year visits, in either eye, while controls (n = 1919) had no evidence for OAG at any visit. All participants had an ocular examination and DNA genotyped for reported OAG risk SNPs. main outcome measure: Incident OAG. RESULTS: Two loci also known to be associated with cup-to-disc ratio as well as OAG (9p21 near CDKN2B-AS1 and SIX1/SIX6) were both significantly associated with incident OAG in the Blue Mountains Eye Study cohort (P = .006 and P = .004, respectively). The TMCO1 locus was nominally associated (P = .012), while the CAV1/CAV2 and 8q22 loci were not associated. Multivariate logistic regression and neural network analysis both indicated that the genetic risk factors contributed positively to the predictive models incorporating traditional risk factors. CONCLUSIONS: This study shows that previously reported genetic variations related to OAG and cup-to-disc ratio are associated with the onset of OAG and thus may become useful in risk prediction algorithms designed to target early treatment to those most at risk of developing glaucoma.

Serum homocysteine, vitamin B12, and folate, and the prevalence and incidence of posterior subcapsular cataract.

PURPOSE: We assessed associations between serum levels of homocysteine, vitamin B12, and folate, and the prevalence and 5-year incidence of posterior subcapsular cataract (PSC) in Blue Mountains Eye Study participants. METHODS: We examined 3508 participants aged 49+ years during 1997 to 2000, including 2334 (75.1% of survivors) original and 1174 (85.2% of those eligible) newly recruited subjects. Five years later (2002-2004), 1952 (76.6% of survivors) original participants were re-examined. Detailed examinations, including lens photographs and fasting blood tests, were conducted at both visits. Logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) after multivariable adjustment. RESULTS: In this population, those with PSC were older, less likely to have higher education, and more likely to have diabetes and myopia. The PSC prevalence was 5.7% (150/2644). Higher levels of homocysteine (per SD; OR, 1.17; 95% CI, 1.00-1.37) and lower levels of folate (per SD; OR, 1.24; 95% CI, 0.99-1.56) were associated with prevalent PSC. There was significant interaction (P < 0.05) between vitamin B12 and homocysteine; for B12 ≥125 pmol/L, 28% higher PSC prevalence was associated with homocysteine (per SD; OR, 1.28; 95% CI, 1.09-1.52); however, for B12 <125 pmol/L, nonsignificant lower PSC prevalence was associated with homocysteine (per SD; OR, 0.16; 95% CI, 0.02-1.57). The 5-year PSC incidence was 5.7% (n = 59/1030) with no significant associations with homocysteine, B12, and folate. CONCLUSIONS: Higher serum homocysteine level was associated with PSC prevalence in this population. Vitamin B12 status seemed to modify this association. Lack of longitudinal association could have resulted from insufficient study power.

Complete blood count and retinal vessel calibers.

OBJECTIVE: The influence of hematological indices such as complete blood count on microcirculation is poorly understood. Retinal microvasculature can be directly visualized and vessel calibers are associated with a range of ocular and systemic diseases. We examined the association of complete blood count with retinal vessel calibers. METHODS: Cross-sectional population-based Blue Mountains Eye Study, n = 3009, aged 49+ years. Complete blood count was measured from fasting blood samples taken at baseline examination, 1992-4. Retinal arteriolar and venular calibers were measured from digitized retinal photographs using a validated semi-automated computer program. RESULTS: All analyses adjusted for age, sex, systolic blood pressure, diabetes, smoking and fellow vessel caliber. Higher hematocrit, white cell count and platelet count were associated with narrower arteriolar caliber (p = 0.02, 0.03 and 0.001 respectively), while higher hemoglobin, hematocrit, red cell count, white cell count and platelet count were associated with wider venular caliber (p<0.0001 for all). Each quintile increase in hematocrit, white cell count and platelet count was associated with approximately 0.5 µm narrower arteriolar caliber; whereas each quintile increase in all of the complete blood count components was associated with approximately 1-2 µm wider venular caliber. CONCLUSIONS: These associations show that elevated levels of hematological indices can have adverse effects on the microcirculation.

Estimated cases of blindness and visual impairment from neovascular age-related macular degeneration avoided in Australia by ranibizumab treatment.

Intravitreal injections of anti-vascular endothelial growth factor agents, such as ranibizumab, have significantly improved the management of neovascular age-related macular degeneration. This study used patient-level simulation modelling to estimate the number of individuals in Australia who would have been likely to avoid legal blindness or visual impairment due to neovascular age-related macular degeneration over a 2-year period as a result of intravitreal ranibizumab injections. The modelling approach used existing data for the incidence of neovascular age-related macular degeneration in Australia and outcomes from ranibizumab trials. Blindness and visual impairment were defined as visual acuity in the better-seeing eye of worse than 6/60 or 6/12, respectively. In 2010, 14,634 individuals in Australia were estimated to develop neovascular age-related macular degeneration who would be eligible for ranibizumab therapy. Without treatment, 2246 individuals would become legally blind over 2 years. Monthly 0.5 mg intravitreal ranibizumab would reduce incident blindness by 72% (95% simulation interval, 70-74%). Ranibizumab given as needed would reduce incident blindness by 68% (64-71%). Without treatment, 4846 individuals would become visually impaired over 2 years; this proportion would be reduced by 37% (34-39%) with monthly intravitreal ranibizumab, and by 28% (23-33%) with ranibizumab given as needed. These data suggest that intravitreal injections of ranibizumab, given either monthly or as needed, can substantially lower the number of cases of blindness and visual impairment over 2 years after the diagnosis of neovascular age-related macular degeneration.

Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium.

PURPOSE: To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). DESIGN: Meta-analysis. METHODS: setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES), and Rotterdam Study (RS). observation procedures: Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. main outcome measures: Incidence of AMD. RESULTS: The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the 3 studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. CONCLUSION: In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD.

Adherence to dietary guidelines and the 10-year cumulative incidence of visual impairment: the Blue Mountains Eye Study.

PURPOSE: To assess whether adherence to dietary guidelines at baseline is associated with the incidence of visual impairment among older persons after 10 years. DESIGN: A population-based cohort of 3654 participants of the Blue Mountains Eye Study were examined at baseline and were reexamined after 5 and 10 years. METHODS: The incidence of visual impairment was defined as best-corrected visual acuity (VA)<20/40 at follow-up in 1 or both eyes. Dietary information was obtained at baseline using a validated food frequency questionnaire (FFQ). Total Diet Score (TDS) was calculated based on the Australian diet quality index. TDS includes components of diet quality; poor dietary habits; and energy balance. Discrete logistic regression models with time-dependant outcome variables were used to calculate hazard risk ratios (HR) and 95% confidence intervals (CI) associated with incidence of visual impairment for each unit/quartile increase in TDS, adjusting for potential confounders. RESULTS: Of the 3654 baseline participants, 1963 had up to 10 years follow-up with completed FFQs. With each unit increase in TDS, the risk of visual impairment decreased (HR 0.94, 95% CI 0.88-1.00). The risk of developing visual impairment was lower among persons in the highest compared to the lowest TDS quartile (HR 0.71, 95% CI 0.47-1.05). This association was significant among persons aged 65+ years (HR 0.63, 95% CI 0.38-0.98) but not those aged <65 years (HR 0.95, 95% CI 0.46-1.97). CONCLUSIONS: Compliance to dietary guidelines was associated with a decreased long-term risk of visual impairment in this sample of Australians aged 65+ years.

Consumption of dairy products and the 15-year incidence of age-related macular degeneration.

Habitual consumption of dairy products has been shown to play an important role in the prevention of several chronic diseases. We aimed to prospectively assess the relationship between the change in dairy product consumption (both regular fat and low/reduced fat) and the 15-year incidence of age-related macular degeneration (AMD). In the Blue Mountains Eye Study, 2037 participants aged 49 years or above at baseline were re-examined at follow-up in 1997-9, 2002-4 and/or 2007-9. AMD was assessed from retinal photographs. Dietary data were collected using a semi-quantitative FFQ, and servings of dairy product consumption calculated. Over the 15-year follow-up, there were 352, 268 and eighty-four incident cases of any, early and late AMD, respectively. After adjusting for age, sex, current smoking, white cell count and fish consumption, a significant linear trend (P for trend = 0·003) was observed with decreasing consumption of total dairy foods and the 15-year incidence of late AMD, comparing the lowest v. highest quintile of intake (OR 2·80, 95 % CI 1·21, 3·04). Over the 15 years, decreased consumption of reduced-fat dairy foods was associated with an increased risk of incident late AMD, comparing the lowest to highest quintile of intake (OR 3·10, 95 % CI 1·18, 8·14, P for trend = 0·04). Decreasing total dietary Ca intake over the 15 years was also associated with an increased risk of developing incident late AMD (multivariable-adjusted P for trend = 0·03). A lower consumption of dairy products (regular and low fat) and Ca was independently associated with a higher risk of developing incident late AMD in the long term. Additional cohort studies are needed to confirm these findings.

Harmonizing the classification of age-related macular degeneration in the three-continent AMD consortium.

PURPOSE: To describe methods to harmonize the classification of age-related macular degeneration (AMD) phenotypes across four population-based cohort studies: the Beaver Dam Eye Study (BDES), the Blue Mountains Eye Study (BMES), the Los Angeles Latino Eye Study (LALES), and the Rotterdam Study (RS). METHODS: AMD grading protocols, definitions of categories, and grading forms from each study were compared to determine whether there were systematic differences in AMD severity definitions and lesion categorization among the three grading centers. Each center graded the same set of 60 images using their respective systems to determine presence and severity of AMD lesions. A common 5-step AMD severity scale and definitions of lesion measurement cutpoints and early and late AMD were developed from this exercise. RESULTS: Applying this severity scale changed the age-sex adjusted prevalence of early AMD from 18.7% to 20.3% in BDES, from 4.7% to 14.4% in BMES, from 14.1% to 15.8% in LALES, and from 7.5% to 17.1% in RS. Age-sex adjusted prevalences of late AMD remained unchanged. Comparison of each center's grades of the 60 images converted to the consortium scale showed that exact agreement of AMD severity among centers varied from 61.0-81.4%, and one-step agreement varied from 84.7-98.3%. CONCLUSION: Harmonization of AMD classification reduced categorical differences in phenotypic definitions across the studies, resulted in a new 5-step AMD severity scale, and enhanced similarity of AMD prevalence among the four cohorts. Despite harmonization it may still be difficult to remove systematic differences in grading, if present.

Fluid intake and all-cause mortality, cardiovascular mortality and kidney function: a population-based longitudinal cohort study.

BACKGROUND: Drinking eight glasses of fluid or water each day is widely believed to improve health, but evidence is sparse and conflicting. We aimed to investigate the association between fluid consumption and long-term mortality and kidney function. METHODS: We conducted a longitudinal analysis within a prospective, population-based cohort study of 3858 men and women aged 49 years or older residing in Australia. Daily fluid intake from food and beverages not including water was measured using a food frequency questionnaire. We did multivariable adjusted Cox proportional hazard models for all-cause and cardiovascular mortality and a boot-strapping procedure for estimated glomerular filtration rate (eGFR). RESULTS: Upper and lower quartiles of daily fluid intake corresponded to >3 L and <2 L, respectively. During a median follow-up of 13.1 years (total 43 093 years at risk), 1127 deaths (26.1 per 1000 years at risk) including 580 cardiovascular deaths (13.5 per 1000 years at risk) occurred. Daily fluid intake (per 250 mL increase) was not associated with all-cause [adjusted hazard ratio (HR) 0.99 (95% CI 0.98-1.01)] or cardiovascular mortality [HR 0.98 (95% CI 0.95-1.01)]. Overall, eGFR reduced by 2.2 mL/min per 1.73 m(2) (SD 10.9) in the 1207 (31%) participants who had repeat creatinine measurements and this was not associated with fluid intake [adjusted regression coefficient 0.06 mL/min/1.73 m(2) per 250 mL increase (95% CI -0.03 to 0.14)]. CONCLUSIONS: Fluid intake from food and beverages excluding water is not associated with improved kidney function or reduced mortality.

Myopia and the long-term incidence of cataract and cataract surgery: the Blue Mountains Eye Study.

BACKGROUND: To assess the association between refractive errors and the 10-year incidence of cataract and cataract surgery. DESIGN: Population-based prospective study. PARTICIPANTS: Three thousand six hundred fifty-four persons aged 49+ years living in a well-defined geographical region were examined at baseline; 2564 were re-examined after 5 and/or 10 years. METHODS: Baseline refractive error was measured using autorefraction with subjective refinement. Lens photographs were taken at each visit and assessed using the Wisconsin Cataract Grading System. MAIN OUTCOME MEASURES: Long-term incidence of cataract and cataract surgery. RESULTS: Compared with emmetropia, high myopia was associated with increased incidence of nuclear cataract (adjusted odds ratio 3.01, 95% confidence intervals 1.35-6.71). Low (odds ratio 1.86, confidence interval 1.03-3.35) and high myopia (odds ratio 7.80, confidence interval 3.51-17.35) were significantly associated with higher incidence of posterior subcapsular cataract. Low, moderate and high myopia were associated with increased incidence of cataract surgery (odds ratio 2.54, confidence interval 1.76-3.68; odds ratio 2.61, confidence interval 1.45-4.69; and odds ratio 4.81, confidence interval 2.33-9.93, respectively). Either any (odds ratio 1.35, confidence interval 1.08-1.69) or moderate hyperopia (odds ratio 1.76, confidence interval 1.32-2.34) was associated with increased incidence of nuclear cataract. CONCLUSION: Our longitudinal study confirms the association between myopia and an increased risk of nuclear and posterior subcapsular cataract. It also suggests that hyperopia may increase the risk of nuclear cataract.

Genetic susceptibility, dietary antioxidants, and long-term incidence of age-related macular degeneration in two populations.

OBJECTIVE: To examine effect modification between genetic susceptibility to age-related macular degeneration (AMD) and dietary antioxidant or fish consumption on AMD risk. DESIGN: Pooled data analysis of population-based cohorts. PARTICIPANTS: Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). METHODS: Dietary intakes of antioxidants (lutein/zeaxanthin [LZ], ß-carotene, and vitamin C), long-chain omega-3 polyunsaturated fatty acids, and zinc were estimated from food frequency questionnaires. The AMD genetic risk was classified according to the number of risk alleles of CFH (rs1061170) or ARMS2 (rs10490924) as low (no or 1 risk allele) or high (≥ 2 risk alleles). Interactions between dietary intake and genetic risk levels were assessed. Associations between dietary intake and AMD risk were assessed comparing the highest with the 2 lower intake tertiles by genetic risk subgroups using discrete logistic regression, conducted in each study separately and then using pooled data. Participants without AMD lesions at any visit were controls. We adjusted for age and sex in analyses of each cohort sample and for smoking status and study site in pooled-data analyses. MAIN OUTCOME MEASURES: All 15-year incident late AMD cases were confirmed by chief investigators of the Beaver Dam Eye Study, BMES, and RS. Intergrader reproducibility was assessed in an early AMD subsample, with 86.4% agreement between BMES and RS graders, allowing for a 1-step difference on a 5-step AMD severity scale. RESULTS: In pooled data analyses, we found significant interaction between AMD genetic risk status and LZ intake (P=0.0009) but nonsignificant interactions between genetic risk status and weekly fish consumption (P=0.05) for risk of any AMD. Among participants with high genetic risk, the highest intake tertile of LZ was associated with a >20% reduced risk of early AMD, and weekly consumption of fish was associated with a 40% reduced risk of late AMD. No similar association was evident among participants with low genetic risk. No interaction was detected between ß-carotene or vitamin C and genetic risk status. CONCLUSIONS: Protection against AMD from greater LZ and fish consumption in persons with high genetic risk based on 2 major AMD genes raises the possibility of personalized preventive interventions.

Incidence and progression of reticular drusen in age-related macular degeneration: findings from an older Australian cohort.

PURPOSE: To assess the 15-year incidence and progression of reticular drusen and associations of this lesion with age-related macular degeneration (AMD) risk factors. DESIGN: Population-based cohort. PARTICIPANTS: Blue Mountains Eye Study participants (n = 3654) 49 years of age and older attended baseline examinations; of these, 75.8%, 76.7%, and 56.1% of survivors attended 5-year, 10-year, and 15-year follow-up examinations, respectively. METHODS: Color retinal photographs were obtained and comprehensive questionnaires were administered at each visit, and DNA samples were genotyped. Fundus autofluorescence images were not available. Reticular drusen identified from photographs were confirmed with side-by-side grading using the Wisconsin AMD grading protocol. Incidence was assessed using Kaplan-Meier product limit survival methods, controlling for competing risk of death. Associations between smoking, fish consumption, serum lipids, systemic and dietary factors, the CFH single nucleotide polymorphism (SNP) rs1061170 and ARMS2 SNP rs10490924, and the 15-year incidence of reticular drusen were analyzed in discrete logistic regression models. Generalized estimating equation models were used to analyze eye-specific relationships between these risk factors and 5-year progression from reticular drusen to late AMD. MAIN OUTCOME MEASURES: Incidence and progression of reticular drusen. RESULTS: The 15-year cumulative incidence of reticular drusen was 4.0% (n = 95). Increasing age (per decade increase; odds ratio [OR], 3.4; 95% confidence interval [CI], 2.6-4.4), female sex (OR, 2.0; 95% CI, 1.3-3.2), and presence of risk alleles of CFH-rs1061170 (OR, 1.8; 95% CI, 1.3-2.4) or ARMS2-rs10490924 (OR, 3.0; 95% CI, 2.1-4.4) were associated with higher reticular drusen incidence. Current smoking at baseline predicted higher reticular drusen incidence (OR 2.1, 95% CI 1.0-4.5) after adjusting for age, sex, CFH-rs1061170 and ARMS2-rs10490924 polymorphisms. Of 118 eyes with reticular drusen, 40 (33.9%) developed late AMD over 5 years. A higher proportion of eyes with reticular drusen located outside versus within the macular area progressed to late AMD (50.0% vs. 37.8%). Dietary lutein-zeaxanthin intake was associated with decreased likelihood of progression from reticular drusen to late AMD (adjusted OR, 0.5; 95% CI, 0.3-1.0). CONCLUSIONS: Known AMD risk factors were associated with greater long-term risk of reticular drusen. Neither total area nor central location of reticular drusen predicted 5-year progression to late AMD. Increased consumption of lutein-zeaxanthin predicted a lower risk of progression.

Differing associations of white matter lesions and lacunar infarction with retinal microvascular signs.

BACKGROUND: White matter lesions (WML) and lacunar infarcts (LI) are believed to have microvascular etiologies but the exact microvascular changes occurring in each is unclear. AIM: Using the retina as a proxy, we assessed retinal microvascular changes in WML and LI. METHODS: We prospectively recruited 1211 acute stroke patients. Four subgroups were identified from neuroimaging: WML alone, LI alone, both WML and LI, neither WML nor LI. Masked retinal photographs identified retinopathy and retinal arteriolar wall signs and measured retinal vascular caliber. RESULTS: Compared with 448 controls with neither WML nor LI, 384 patients with only WML were more likely to have retinopathy [odds ratio (OR) 1·5, 95% confidence interval (CI) 1·1 to 2·1] and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·1 to 2·3); 200 patients with only LI were more likely to have arteriolar narrowing (OR 1·6, 95% CI 1·1 to 2·3) and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·0 to 2·4); and 179 patients with both WML and LI were more likely to have arteriovenous nicking (OR 1·7, 95% CI 1·1 to 2·6), enhanced arteriolar light reflex (OR 2·0, 95% CI 1·3 to 3·2) and wider venules (OR 2·3, 95% CI 1·4 to 3·6). All analyses were adjusted for age, gender, study site and cardiovascular risk factors. CONCLUSION: Both WML and LI were associated with retinal microvascular signs, supporting a microvascular etiology. Differing patterns of association suggest different mechanisms may predominate, e.g. greater endothelial permeability in WML, and ischemia associated with arteriolar wall disease in LI.

Patients' Short-term Satisfaction With Cataract Surgery and Long-Term Sustainability of Improved Visual-Related Quality of Life Over 3 Postoperative Years.

PURPOSE: This study aimed to assess self-reported satisfaction following cataract surgery, and the sustainability of improved visual function and health-related quality of life in a cataract surgical cohort over 3 years post-phacoemulsification surgery. DESIGN: A clinic-based cohort study. METHODS: Cataract surgical patients were recruited and followed up annually after surgery. Logarithm of the minimum angle of resolution (LogMAR) visual acuity, visual function (using the VF-14 questionnaire), and health-related quality of life (using the Short-Form Health Survey [SF-36] questionnaire) were assessed preoperatively and at 1, 2, and 3 years postoperatively. RESULTS: Of the 2029 patients recruited, 1924 (94.8%) had at least 1 postoperative visit, and 1229 (63.9%) had the 3-year follow-up examination performed. The mean age was 75.1 ± 6 years, and 54.1% were female. Of the 1229, 439 (35.7%) and 286 (23.3%) had completed the VF-14 and SF-36 questionnaires, respectively, at all 3 follow-up visits. The majority (92.1%) of patients reported being satisfied with the outcome of the surgery 6 months postoperatively. The overall VF-14 scores were significantly improved at the 12-month postoperative visits compared with preoperative scores (P < 0.01), independent of age and sex. The improved VF-14 mean scores were sustained for up to 3 years postoperatively. Health-related quality of life (SF-36 scores) showed no significant changes between preoperative and 1-, 2-, and 3-year postoperative examinations. CONCLUSIONS: We documented the sustainability of improvement in visual function-related quality of life associated with cataract surgery over 3 postoperative years. Cataract surgery was not associated with improvement in health-related quality-of-life scores.

Three-year incidence and factors associated with posterior capsule opacification after cataract surgery: The Australian Prospective Cataract Surgery and Age-related Macular Degeneration Study.

PURPOSE: To assess 3-year incidence and associated factors of posterior capsule opacification (PCO) after phacoemulsification surgery. DESIGN: Cohort study. METHODS: A total of 1934 consecutive patients aged ≥64 years undergoing phacoemulsification surgery at Westmead Hospital were recruited, of whom 1495 (77.3%) had retroillumination anterior segment images taken of the surgical eyes after 1 month and at a further postoperative visit within 3 years. Severe PCO was defined if the view of the optic disc was obscured, or neodymium-yttrium-aluminum-garnet capsulotomy was performed. Cumulative incidence of PCO was estimated using Kaplan-Meier methods. Associations of PCO with surgeon groups and different types of implanted intraocular lenses (IOLs) were assessed, adjusting for age, sex, diabetes, and ethnicity. RESULTS: Three-year cumulative incidence of PCO was 38.5% (95% confidence interval [CI] 36.1%-40.9%) among the 1495 patients, including 4.7% (95% CI 3.5%-5.8%) with severe PCO. PCO incidence was higher in: (1) eyes operated on by junior trainees (49%) compared to those by senior ophthalmologist surgeons (36%) (adjusted odds ratio [OR] 1.6, 95% CI 1.2-2.0); and (2) eyes with hydrophobic, 3-piece (either square-edged [51%, OR 2.3, 95% CI 1.4-3.6] or partial-round-edged [39%, OR 1.5, 95% CI 1.1-2.1]), or hydrophilic IOLs (64%, OR 2.9, 95% CI 1.9-4.4) compared to those with single-piece, square-edged, hydrophobic IOLs (34%), after additional adjustment for surgeon group. CONCLUSIONS: Predominantly mild PCO occurred in one-third of eyes after phacoemulsification surgery. Possible predisposing factors associated with PCO development include surgery performed by ophthalmologic trainees and the use of hydrophilic or other hydrophobic IOLs apart from the single-piece, square-edged one.

Visual impairment corrected via cataract surgery and 5-year survival in a prospective cohort.

PURPOSE: To compare mortality risk between cataract surgical patients with corrected and persistent visual impairment. DESIGN: Cohort study. METHODS: A total of 1864 consecutive patients, aged ≥64 years, undergoing phacoemulsification surgery at Westmead Hospital were followed annually for 5 years postoperatively. Visual impairment status in the surgical eye was categorized as none (presenting visual acuity [VA], ≥20/40), mild (VA <20/40-20/60), or moderate-severe (VA <20/60). All-cause mortality was obtained from the Australian National Death Index. RESULTS: Of 901 patients with moderate-severe visual impairment before surgery, 60.4% (n = 544), 15.5% (n = 140), and 24.1% (n = 217) had no, mild, or moderate-severe visual impairment in the surgical eye, respectively, 1 month postoperatively. Age-standardized 5-year mortality rates were nonsignificantly lower in patients with either mild (24.7%, 95% confidence interval [CI] 16.5%-32.9%) or no visual impairment (24.1%, 95% CI 19.9%-28.4%) post surgery compared to that in patients whose moderate-severe visual impairment persisted (30.6%, 95% CI 23.3%-37.9%). After adjusting for age, sex, smoking, body mass index, and individual comorbid conditions, such as hypertension, diabetes, angina, myocardial infarction, stroke, transient ischemic attack, and kidney disease, patients with no visual impairment 1 month postoperatively had a lower mortality risk (HR 0.73, 95% CI 0.52-1.01) compared to those with persistent moderate-severe visual impairment after surgery. This finding was significant (HR 0.71, 95% CI 0.51-0.99) after additional adjustment for number of medications taken (continuous variable) and number (≥3 vs <3) of comorbid conditions. CONCLUSION: Correcting moderate-severe visual impairment in older patients with phacoemulsification surgery was associated with a lower mortality risk, compared to surgical patients whose visual impairment persisted postoperatively.

Prediction of age-related macular degeneration in the general population: the Three Continent AMD Consortium.

PURPOSE: Prediction models for age-related macular degeneration (AMD) based on case-control studies have a tendency to overestimate risks. The aim of this study is to develop a prediction model for late AMD based on data from population-based studies. DESIGN: Three population-based studies: the Rotterdam Study (RS), the Beaver Dam Eye Study (BDES), and the Blue Mountains Eye Study (BMES) from the Three Continent AMD Consortium (3CC). PARTICIPANTS: People (n = 10,106) with gradable fundus photographs, genotype data, and follow-up data without late AMD at baseline. METHODS: Features of AMD were graded on fundus photographs using the 3CC AMD severity scale. Associations with known genetic and environmental AMD risk factors were tested using Cox proportional hazard analysis. In the RS, the prediction of AMD was estimated for multivariate models by area under receiver operating characteristic curves (AUCs). The best model was validated in the BDES and BMES, and associations of variables were re-estimated in the pooled data set. Beta coefficients were used to construct a risk score, and risk of incident late AMD was calculated using Cox proportional hazard analysis. Cumulative incident risks were estimated using Kaplan-Meier product-limit analysis. MAIN OUTCOME MEASURES: Incident late AMD determined per visit during a median follow-up period of 11.1 years with a total of 4 to 5 visits. RESULTS: Overall, 363 participants developed incident late AMD, 3378 participants developed early AMD, and 6365 participants remained free of any AMD. The highest AUC was achieved with a model including age, sex, 26 single nucleotide polymorphisms in AMD risk genes, smoking, body mass index, and baseline AMD phenotype. The AUC of this model was 0.88 in the RS, 0.85 in the BDES and BMES at validation, and 0.87 in the pooled analysis. Individuals with low-risk scores had a hazard ratio (HR) of 0.02 (95% confidence interval [CI], 0.01-0.04) to develop late AMD, and individuals with high-risk scores had an HR of 22.0 (95% CI, 15.2-31.8). Cumulative risk of incident late AMD ranged from virtually 0 to more than 65% for those with the highest risk scores. CONCLUSIONS: Our prediction model is robust and distinguishes well between those who will develop late AMD and those who will not. Estimated risks were lower in these population-based studies than in previous case-control studies.

Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.