Characterization of a Novel Splicing Variant in Acylglycerol Kinase (AGK) Associated with Fatal Sengers Syndrome.

Mitochondrial functional integrity depends on protein and lipid homeostasis in the mitochondrial membranes and disturbances in their accumulation can cause disease. AGK, a mitochondrial acylglycerol kinase, is not only involved in lipid signaling but is also a component of the TIM22 complex in the inner mitochondrial membrane, which mediates the import of a subset of membrane proteins. AGK mutations can alter both phospholipid metabolism and mitochondrial protein biogenesis, contributing to the pathogenesis of Sengers syndrome. We describe the case of an infant carrying a novel homozygous AGK variant, c.518+1G>A, who was born with congenital cataracts, pielic ectasia, critical congenital dilated myocardiopathy, and hyperlactacidemia and died 20 h after birth. Using the patient's DNA, we performed targeted sequencing of 314 nuclear genes encoding respiratory chain complex subunits and proteins implicated in mitochondrial oxidative phosphorylation (OXPHOS). A decrease of 96-bp in the length of the AGK cDNA sequence was detected. Decreases in the oxygen consumption rate (OCR) and the OCR:ECAR (extracellular acidification rate) ratio in the patient's fibroblasts indicated reduced electron flow through the respiratory chain, and spectrophotometry revealed decreased activity of OXPHOS complexes I and V. We demonstrate a clear defect in mitochondrial function in the patient's fibroblasts and describe the possible molecular mechanism underlying the pathogenicity of this novel AGK variant. Experimental validation using in vitro analysis allowed an accurate characterization of the disease-causing variant.

Mortality during 6 years of follow-up in relation to visual impairment and eye disease: results from a population-based cohort study of people aged 50 years and above in Nakuru, Kenya.

OBJECTIVE: To estimate the association between (1) visual impairment (VI) and (2) eye disease and 6-year mortality risk within a cohort of elderly Kenyan people. DESIGN, SETTING AND PARTICIPANTS: The baseline of the Nakuru Posterior Segment Eye Disease Study was formed from a population-based survey of 4318 participants aged ≥50 years, enrolled in 2007-2008. Ophthalmic and anthropometric examinations were undertaken on all participants at baseline, and a questionnaire was administered, including medical and ophthalmic history. Participants were retraced in 2013-2014 for a second examination. Vital status was recorded for all participants through information from community members. Cumulative incidence of mortality, and its relationship with baseline VI and types of eye disease was estimated. Inverse probability weighting was used to adjust for non-participation. PRIMARY OUTCOME MEASURES: Cumulative incidence of mortality in relation to VI level at baseline. RESULTS: Of the baseline sample, 2170 (50%) were re-examined at follow-up and 407 (10%) were known to have died (adjusted risk of 11.9% over 6 years). Compared to those with normal vision (visual acuity (VA) ≥6/12, risk=9.7%), the 6-year mortality risk was higher among people with VI (<6/18 to ≥6/60; risk=28.3%; risk ratio (RR) 1.75, 95% CI 1.28 to 2.40) or severe VI (SVI)/blindness (<6/60; risk=34.9%; RR 1.98, 95% CI 1.04 to 3.80). These associations remained after adjustment for non-communicable disease (NCD) risk factors (mortality: RR 1.56, 95% CI 1.14 to 2.15; SVI/blind: RR 1.46, 95% CI 0.80 to 2.68). Mortality risk was also associated with presence of diabetic retinopathy at baseline (RR 3.18, 95% CI 1.98 to 5.09), cataract (RR 1.26, 95% CI 0.95 to 1.66) and presence of both cataract and VI (RR 1.57, 95% CI 1.24 to 1.98). Mortality risk was higher among people with age-related macular degeneration at baseline (with or without VI), compared with those without (RR 1.42, 95% CI 0.91 to 2.22 and RR 1.34, 95% CI 0.99 to 1.81, respectively). CONCLUSIONS: Visual acuity was related to 6-year mortality risk in this cohort of elderly Kenyan people, potentially because both VI and mortality are related to ageing and risk factors for NCD.

Long-term outcomes after allogeneic stem cell transplantation for children with hematological malignancies.

We analyzed long-term outcomes and psycho-social aspects in 112 children with malignancies surviving 1 year after hematopoietic stem cell transplantation. At 10 years, overall survival was 75+/-5%, TRM 18+/-4% and relapse 14+/-3%; 10-year cumulative incidence of infections was 31+/-4%, cataract 44+/-4%, pulmonary dysfunction 20+/-4%, bone and joint complications 29+/-5%, hypothyroidism 36+/-4%, cardiac complications 11+/-3% and secondary malignancies 7+/-3%. Total body irradiation (TBI) was the most significant risk factor associated with cataract, pulmonary impairment, osteoarticular complications and hypothyroidism. Chronic graft-versus-host disease was associated with higher incidence of pulmonary dysfunction. The number of complications per patient increased with time. Half of the patients had psychological disturbance, 13 signs of depression and 16 a history of eating behavior disorders; 54% of patients with one or more long-term complications had psychological problems. Sixty-nine patients had learning difficulties and 36 achieved normal scholarship. With increased follow-up, development of late effects and of psycho-social disturbance are of major concern. While the use of single-dose TBI has now been abandoned, other risk factors are still of concern in the early 2000s.

Visual impairment, age-related macular degeneration, cataract, and long-term mortality: the Blue Mountains Eye Study.

OBJECTIVE: To assess the association of visual impairment, age-related macular degeneration (ARMD), and cataract with long-term mortality. METHODS: At baseline, 3654 persons 49 years and older were examined in the Blue Mountains Eye Study (1992-1994). Standardized photographic grading was used to assess ARMD and cataract. Mortality and causes of death occurring between baseline and December 31, 2003, were obtained via data linkage with the Australian National Death Index. Age-standardized mortality rates were calculated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were assessed using Cox models. Result Age-standardized mortality was higher in persons with vs without visual impairment (54.0% vs 34.0%), ARMD (45.8% vs 33.7%), and cataract (39.2% vs 29.5%). After adjusting for factors that predict mortality, neither visual impairment (HR, 1.3; 95% CI, 0.98-1.7) nor ARMD (HR, 1.0; 95% CI, 0.8-1.3) was significantly associated with all-cause mortality in all ages. Among persons younger than 75 years, however, ARMD predicted higher all-cause mortality (HR, 1.6; 95% CI, 1.0-2.4). Any cataract (HR, 1.3; 95% CI, 1.0-1.5) and cortical (HR, 1.2; 95% CI, 0.97-1.4), nuclear (HR, 1.2; 95% CI, 0.98-1.5), and posterior subcapsular (HR, 1.3; 95% CI, 1.0-1.7) cataract were also associated with higher all-cause mortality. CONCLUSION: Cataract predicted increased mortality in persons 49 years and older, and ARMD predicted mortality in persons aged 49 to 74 years.

Effect of individual-level and socioeconomic factors on long-term survival after cataract surgery over a 30-year period.

PURPOSE: To evaluate survival and the risk for mortality after cataract surgery in relation to individual-level and socioeconomic factors in Scotland over 3 decades. SETTING: Linked healthcare data, United Kingdom. DESIGN: Representative population-based study. METHODS: A 5% random sample of Scottish decedents linked to hospital records (1981 to 2012) was assessed. Survival time, survival probability, and determinants of mortality were evaluated after the first and second recorded hospital episodes for cataract surgery. Cox proportional-hazards regression models were used to assess the effect of individual-level and socioeconomic factors including age, geographic location, socioeconomic status, and comorbidity on mortality. RESULTS: The study evaluated linked administrative healthcare data from 9228 deceased patients who had cataract surgery. The mean survival time was 2383 days ± 1853 (SD). The survival probability decreased from 98% 90 days after surgery to 22% at 10 years, 2% at 20 years, and 0% after 30 years. The mean age was 77 ± 9 years. Age (hazard ratio [HR] 3.66; 95% confidence interval [CI], 2.97-3.80; P < .001) and severe comorbidity (HR 1.68; 95% CI, 1.47-1.91; P < .001) were associated with an increased risk for mortality; women had a 20% lower risk than men (HR 0.80; 95% CI, 0.76-0.83; P < .001). Socioeconomic status and rural geographic locations were not linked to mortality. CONCLUSIONS: Long-term survival after cataract surgery was determined by individual-level characteristics reflecting the mortality patterns of aging populations. The mortality risk was independent of socioeconomic and geographic factors per se.

Age-related eye disease, visual impairment, and survival: the Beaver Dam Eye Study.

OBJECTIVE: To investigate the relationship of age-related maculopathy, cataract, glaucoma, visual impairment, and diabetic retinopathy to survival during a 14-year period. METHODS: Persons ranging in age from 43 to 84 years in the period from September 15, 1987, to May 4, 1988, participated in the baseline examination of the population-based Beaver Dam Eye Study (n = 4926). Standardized protocols, including photography, were used to determine the presence of ocular disease. Survival was followed using standardized protocols. RESULTS: As of December 31, 2002, 32% of the baseline population had died (median follow-up, 13.2 years). After adjusting for age, sex, and systemic and lifestyle factors, poorer survival was associated with cortical cataract (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.06-1.37), any cataract (HR, 1.16; 95% CI, 1.03-1.32), diabetic retinopathy (HR per 1-step increase in 4-level severity, 1.36; 95% CI, 1.14-1.63), and visual impairment (HR, 1.24; 95% CI, 1.04-1.48) and marginally associated with increasing severity of nuclear sclerosis (HR, 1.07; 95% CI, 0.99-1.16). Age-related maculopathy and glaucoma were not associated with poorer survival. Associations tended to be slightly stronger in men than women. CONCLUSIONS: Cataract, diabetic retinopathy, and visual impairment were associated with poorer survival and not explained by traditional risk factors for mortality. These ocular conditions may serve as markers for mortality in the general population.

Cataract-Related Visual Impairment Corrected by Cataract Surgery and 10-Year Mortality: The Liwan Eye Study.

PURPOSE: To assess 10-year mortality in people who had undergone cataract surgery with no residual visual impairment (VI) and those who had persistent VI due to cataract using a population-based cohort. METHODS: The Liwan Eye Study is a 10-year longitudinal study commenced in 2003. According to the World Health Organization, presenting VI was defined as visual acuity less than 20/63 in the better-seeing eye. History of cataract surgery was defined as cataract surgery performed on either eye. Information on the date of surgery was recorded. Dates of death occurring between baseline and April 30, 2014 were obtained from the National Death Index data. Information on socioeconomic factors was obtained from questionnaire interviews. Cox proportional hazards regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Fifty-nine participants had undergone cataract surgery without residual VI and 67 participants had persistent cataract-related VI. The 10-year mortality rate for participants who had undergone cataract surgery without residual VI was statistically significant lower than that in participants who had VI due to cataract based on log-rank test (32.2% vs. 64.2%; P = 0.002). This finding remained significant in the unadjusted Cox proportional hazards model (HR, 0.43; 95% CI, 0.25-0.74; P = 0.002). After adjusting for age, sex, history of diabetes, and hypertension, body mass index (BMI), education level, and personal income, participants with cataract surgery and no residual VI did not have a higher chance of survival than participants with persistent VI due to cataract (HR, 0.56; 95% CI, 0.26-1.20; P = 0.136). CONCLUSIONS: Cataract-related VI corrected by cataract surgery was not associated with better survival after adjusting for a number of possible confounders. Given our sample size is relatively small and limited power, further studies with larger sample are needed.

Combined effect of probucol and insulin on cataracts of diabetic rats fed a high cholesterol diet.

We investigated the effects of long-term treatment with probucol, a hypolipidemic agent with antioxidative action, insulin, or their combination on cataracts of streptozotocin-induced diabetic rats fed a high cholesterol diet. Each rat was checked for cataracts at 0, 1, 2, 4, 8, 12 and 15 weeks after streptozotocin injection. Cataracts were observed from 8 weeks in untreated hypercholesterolemic and diabetic rats and the incidence of catarats increased to 100% by 15 weeks. The incidence of cataracts in rats treated with probucol, insulin and their combination was first seen at 12, 12 and 15 weeks, respectively, and was 86%, 63% and 33%, respectively, at 15 weeks. The preventive effects of both agents alone and their combination on the cataracts were confirmed by histopathological evaluation of eyeballs. The combined treatment with both agents markedly improved hyperglycemia, hyperlipidemia and increased serum lipid peroxide levels. These results indicate that the combined treatment with probucol and insulin is useful in preventing the development and progression of diabetic cataracts.

Age-related eye disease and survival. The Beaver Dam Eye Study.

OBJECTIVE: To investigate the relationship of cataract, age-related maculopathy, glaucoma, and visual impairment to survival in the population-based Beaver Dam Eye Study. DESIGN: In this population-based study, visual acuity was measured with use of standardized protocols. At baseline, stereoscopic color fundus photographs and color slit-lamp and retroillumination photographs were graded in a masked fashion to determine the presence of age-related maculopathy and cataract, respectively. Deaths were ascertained by contacting family members, daily review of obituaries, and use of vital status records. PARTICIPANTS: Subjects aged 43 through 84 years who lived in Beaver Dam, Wis, were identified and examined between 1988 and 1990. RESULTS: From the time of the baseline examination until a median of 4 years later, 9.5% (467/4926) of the population had died. After correcting for age and sex, poorer survival was associated with more severe nuclear sclerosis (5-year survival of 88.9% for the most severe compared with 94.1% for the least severe stage) and visual impairment (5-year survival of 87.5% for impaired compared with 91.8% for unimpaired vision). However, after controlling for systemic factors, only more severe nuclear sclerosis in people without diabetes was significantly associated with poorer survival (hazard ratio per level of severity, 1.19; 95% confidence interval, 1.00 to 1.40). CONCLUSIONS: These data suggest that after controlling for age and sex, nuclear sclerotic cataract severity, cataract surgery, and visual impairment are risk indicators for poorer survival. Cortical cataract, posterior subcapsular cataract, glaucoma, and age-related maculopathy were unrelated to poorer survival.

Cataract and survival in an elderly nondiabetic population.

Follow-up ranging between 6 and 8 years of the survival of a cohort of 473 elderly nondiabetic subjects randomly selected from a small English town showed an age- and sex-adjusted association between nuclear cataract at the time of baseline examination and decreased survival (P = .002). Comparing those with and without nuclear cataract, the adjusted relative hazard for death was 1.52 (95% confidence interval, 1.15 to 1.99). This effect remained virtually unchanged when also adjusted for whether the subject reported ever having been a smoker.

Visual impairment, age-related cataract, and mortality.

OBJECTIVE: To explore associations between visual impairment, cataract, and mortality in older persons after adjusting for other factors associated with mortality. METHODS: A population cohort of 3654 persons aged 49 years or older (82.4% of eligible residents in the Blue Mountains region, west of Sydney, Australia), were examined at the Blue Mountains Eye Study baseline period (1992-1994) and followed up 5 years later (1997-1999). Australian National Death Index data were used to confirm persons who had died since baseline. Associations between mortality and presence of visual impairment and cataract at baseline were assessed using the Cox proportional hazards regression model, controlling for age, sex, demographic and socioeconomic status, medical history, and health risk behaviors. RESULTS: By June 30, 1999, 604 participants (16.5%) had died. The age- and sex-standardized 7-year cumulative mortality rate was 26% among persons with any visual impairment and 16% in persons without visual impairment. After adjusting for factors found significantly associated with mortality, including age, male sex, low self-rated health, low socioeconomic status, systemic medical conditions, and negative health risk behaviors, the presence at baseline of any visual impairment was independently associated with increased mortality risk (risk ratio [RR], 1.7; 95% confidence interval, 1.2-2.3). The presence of age-related cataract, either nuclear (RR, 1.5), cortical (RR, 1.3), or posterior subcapsular cataract (RR, 1.5), was also significantly associated with increased mortality risk. These associations remained statistically significant when visual impairment and each type of cataract were included simultaneously in the multivariate Cox model. CONCLUSION: Visual impairment and age-related cataract may be independent risk factors for increased mortality in older persons.

Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study: AREDS Report No. 13.

OBJECTIVE: To assess the association of ocular disorders and high doses of antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS). METHODS: Baseline fundus and lens photographs were used to grade the macular and lens status of AREDS participants. Participants were randomly assigned to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Risk of all-cause and cause-specific mortality was assessed using adjusted Cox proportional hazards models. RESULTS: During median follow-up of 6.5 years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models, participants with advanced age-related macular degeneration (AMD) compared with participants with few, if any, drusen had increased mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08-1.86). Advanced AMD was associated with cardiovascular deaths. Compared with participants having good acuity in both eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality (RR, 1.36; 95% CI, 1.12-1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12-1.75) and cataract surgery (RR, 1.55; 95% CI, 1.18-2.05) were associated with increased all-cause mortality and with cancer deaths. Participants randomly assigned to receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61-0.89). CONCLUSIONS: The decreased survival of AREDS participants with AMD and cataract suggests that these conditions may reflect systemic rather than only local processes. The improved survival in individuals randomly assigned to receive zinc requires further study.

Mixed lens opacities and subsequent mortality.

BACKGROUND: Previous studies have found an association between cataract or lens opacity and increased risk of mortality. Further work on determining explanatory factors for this association is needed. OBJECTIVES: To determine, in a population-based cohort of older persons, the 2-year risk of death associated with different types of lens opacities; whether an association of mortality and lens opacity is explained by confounding risk factors such as smoking, diabetes, age, race, and sex, which are known to be related to opacity and mortality; whether lens opacity is a marker for health status; and whether there are differences in cause-specific mortality for persons with and without lens opacity. MAIN OUTCOME MEASURE: Two-year mortality rate. METHODS: The Salisbury Eye Evaluation Project consists of a random sample of 2520 residents of Salisbury, Md, aged 65 to 84 years. At baseline, lens photographs were taken to document nuclear, cortical, posterior subcapsular cataract, and mixed opacities. Data on education, smoking, alcohol use, hypertension, diabetes and other comorbid conditions, handgrip strength, and body mass index were also collected. Two-year follow-up was conducted for mortality and cause of death. RESULTS: Nuclear opacity, particularly severe nuclear opacity, and mixed opacities with nuclear were significant predictors of mortality independent of body mass index, comorbid conditions, smoking, age, race, and sex (mixed nuclear: odds ratio, 2.23; 95% confidence interval, 1.26-3.95). CONCLUSION: Lens opacity status is an independent predictor of 2-year mortality, an association that could not be explained by potential confounders.

Cataract patients in a defined Swedish population 1986-90: VII Inpatient and outpatient standardised mortality ratios.

AIMS: Cataract surgery has at times been said to correlate with an increased death risk. We have therefore analysed the standardised death ratio in a population based cohort of patients that had undergone cataract surgery. METHODS: Data for all patients undergoing cataract surgery from 1986 up to and including 1990 in the Lund Health Care District were prospectively recorded, and 5120 were retrieved for analysis. Death dates and primary death diagnoses for each patient were obtained from the Swedish Bureau of Census up to and including 1991. Standardised mortality ratios were calculated for all patients, subdivided into a number of categories: inpatients, outpatients, sex, age < 75 years, age > or = 75 years, patients with heart and circulatory diseases, with malignant tumours, and with diabetes. The cut off age was set at 74 because this divided the patients into two approximately equal groups. Using time dependent survival regression, the relative risk for dying were estimated for sex, age, and for postoperative YAG laser capsulotomy, and also for diabetic patients and patients with rheumatoid arthritis. RESULTS: Inpatients almost always show an increased standardised mortality ratio compared with outpatients. Young patients and diabetic patients also showed an increased standardised mortality ratio, compared with the normal population, but not older patients, who constitute the majority. Cardiovascular death diagnoses were overrepresented among the young. CONCLUSIONS: Cataract surgery is correlated with an increased standardised mortality ratio only in young patients and in patients with certain complicating diseases like diabetes and cardiovascular diseases.

Increased mortality in women with cataract: a population based follow up of the North London Eye Study.

BACKGROUND/AIMS: In diabetics, cataract is associated with higher risk of death. In non-diabetics the data are conflicting, but some indicate an association between one type of cataract (nuclear) and increased mortality. The aim of this study was to estimate and compare age and sex specific mortality for elderly people with and without cataract in a population based cohort. METHODS: A random sample drawn from a defined population of elderly people (age 65 and older) registered with 17 general practice groups in north London formed the study cohort and were followed up for 4 years. The age and sex specific mortality from various causes was estimated and compared in those with and without cataract. RESULTS: In non-diabetics (n=1318), cataract (lens opacity at baseline) was significantly associated with higher mortality in women. The age standardised death rate per 1000 was 39.8 and 24.8 in women with and without cataract, respectively (age adjusted hazard ratio 1.7, confidence limits 1.1 to 2.7, p=0.032). This was not the case in non-diabetic men (hazard ratio 0.9, confidence limits 0.6 to 1.5, p=0.782). The excess mortality in women with cataract was consistent for cardiovascular, respiratory, and other non-cancer causes of death. There was no association between cataract and mortality from cancer. CONCLUSIONS: This study has shown, for the first time, that cataract is associated with higher mortality in women but not in men, among the non-diabetic population. This sex effect suggests that women may be exposed to risk factors that increase both the risk of cataract and mortality, and that men may have little or no exposure to these "sex specific" factors. Possible risk factors that warrant further investigation may be those associated with some pregnancy and childbearing experience.

The association between cataract and mortality among older adults.

CONTEXT: Previous research has suggested that persons with cataract have an increased risk of death. OBJECTIVE: To compare the mortality experience of patients with cataract who elect surgery, patients with cataract who do not elect surgery, and patients without cataract independent of potentially confounding risk factors. DESIGN: Cohort study. SETTING: Ophthalmology and optometry clinics affiliated with the Callahan Eye Foundation Hospital in Birmingham, Alabama. PATIENTS: 384 persons with and without cataract. MAIN OUTCOME MEASURE: Mortality. RESULTS: Of the 384 study subjects, 286 had cataract, of whom 200 elected to have cataract surgery. Patients with cataract who did and did not elect surgery had significantly higher mortality compared to those without cataract (crude mortality rate ratio (MRR) 3.9 (95% confidence interval (CI) 1.5-9.8) and 7.3 (95% CI 2.8-19.1), respectively). After adjustment for age, gender, race, education, chronic medical conditions, smoking, drinking, depression, and cognitive status, the no-surgery cataract group had an elevated mortality rate (MRR 3.2 (95% 1.2-9.0)), compared to the no-cataract group, with a borderline elevation in MR for the surgery group (MRR 2.0 (95% 0.8-5.9). Limiting the study population to non-diabetics or those without concurrent eye conditions (glaucoma, maculopathy, retinopathy) did not materially influence the adjusted MRRs although the precision of the estimates was reduced. CONCLUSIONS: The results suggest that older persons with cataract, in particular those who decline surgery, have an increased risk of death, supporting the hypothesis that age-related cataract reflects systemic as well as localized ocular disease.

Baseline self-reported cataract and subsequent mortality in Physicians' Health Study I.

PURPOSE: To examine whether a reported history of cataract, a possible marker of aging, is associated with future mortality. METHODS: Participants were 18,669 of the 22,071 U.S. male physicians enrolled in the Physicians' Health Study I who had complete information at study entry, including self-report of presence or absence of baseline cataract. Participants were without a previous history of myocardial infarction, stroke, transient cerebral ischemia, or cancer (except non-melanoma skin cancer). Reported deaths were confirmed by an End Points Committee of physicians. RESULTS: A total of 581 participants reported a personal history of cataract at baseline. During an average of 12.4 years of follow-up, there were 1,514 deaths including 496 due to cardiovascular (CV) and 1,018 due to non-CV causes. After adjustment for differences in age, men who reported cataract at baseline had a non-significant 9% increased risk of death from any cause compared to men who did not report cataract (RR, 1.09; 95% CI, 0.91-1.30). The RRs were 1.03 (95% CI, 0.75-1.41) for CV death and 1.12 (95% CI, 0.90-1.40) for non-CV death. Adjustment for other risk factors had little effect on these estimates. Similar results were obtained in analyses conducted separately among those with and without self-reported diabetes at baseline. CONCLUSIONS: These results from a population of generally healthy physicians indicate that a report of a history of cataract is not associated with any material increase in mortality after adjustment for differences in age between men with and without cataract. Additional investigation of this cohort is in progress to determine whether incident age-related cataracts as well as their subtypes, confirmed by medical record review, are associated with increased mortality.

Age-related cataract, cataract surgery and subsequent mortality: a systematic review and meta-analysis.

PURPOSE: Changes in lens may reflect the status of systemic health of human beings but the supporting evidences are not well summarized yet. We aimed to determine the relationship of age-related cataract, cataract surgery and long-term mortality by pooling the results of published population-based studies. METHODS: We searched PubMed and Embase from their inception till March, 2014 for population-based studies reporting the associations of any subtypes of age-related cataract, cataract surgery with all-cause mortality. We pooled the effect estimates (hazards ratios [HRs]) under a random effects model. RESULTS: Totally, we identified 10 unique population-based studies including 39,659 individuals at baseline reporting the associations of any subtypes of cataract with all-cause mortality from 6 countries. The presence of any cataract including cataract surgery was significantly associated with a higher risk of death (pooled HR: 1.43, 95% CI, 1.21, 2.02; P<0.001; I(2) = 64.2%). In the meta-analysis of 9 study findings, adults with nuclear cataract were at higher risks of mortality (pooled HR: 1.55, 95% CI, 1.17, 2.05; P = 0.002; I(2) = 89.2%). In the meta-analysis of 8 study findings, cortical cataract was associated with higher risks of mortality (pooled HR: 1.26, 95% CI, 1.12, 1.42; P<0.001, I(2) = 29.7%). In the meta-analysis of 6 study findings, PSC cataract was associated with higher risks of mortality (pooled HR: 1.37, 95% CI, 1.04, 1.80; P = 0.03; I(2) = 67.3%). The association between cataract surgery and mortality was marginally non-significant by pooling 8 study findings (pooled HR: 1.27, 95% CI, 0.97, 1.66; P = 0.08; I(2)= 76.6%). CONCLUSIONS: All subtypes of age-related cataract were associated with an increased mortality with nuclear cataract having the strongest association among the 3 cataract subtypes. However, cataract surgery was not significantly related to mortality. These findings indicated that changes in lens may serve as markers for ageing and systemic health in general population.

Ocular diseases and 10-year mortality: the Beijing Eye Study 2001/2011.

PURPOSE: To examine the relationship between major ocular diseases and mortality. METHODS: The population-based longitudinal study Beijing Eye Study was performed in 2001 and repeated in 2011. The participants underwent a detailed ophthalmic examination at baseline in 2001. RESULTS: Of 4439 subjects examined in 2001, 2695 (60.7%) subjects returned for the follow-up examination in 2011, while 379 (8.5%) subjects were dead and 1365 (30.8%) subjects were alive, however, did not agree to be re-examined. In multivariate regression analysis, mortality was significantly associated with the systemic parameters of older age (p < 0.001; Odds ratio (OR): 1.07; 95% confidence interval (CI): 1.05, 1.09), male gender (p < 0.001; OR: 0.56; 95% CI: 0.40, 0.78), lower level of education (p < 0.001; OR: 0.66; 95% CI: 0.59, 0.74) and smoking (p < 0.001; OR: 1.84; 95% CI: 1.36, 2.49) and with the ocular parameters of presence of diabetic retinopathy (p = 0.002; OR: 2.26; 95% CI: 1.34, 3.81), non-glaucomatous optic nerve damage (p = 0.001; OR: 4.90; 95% CI: 1.90, 12.7) and higher degree of nuclear cataract (p = 0.002; OR: 1.29; 95% CI: 1.10, 1.52). In that model, mortality was not significantly (all p > 0.05) associated with refractive error, cortical or subcapsular posterior cataract, intraocular pressure, best corrected visual acuity, visual field defects, prevalence of age-related macular degeneration, retinal vein occlusions, open-angle glaucoma and angle-closure glaucoma. CONCLUSIONS: After adjustment for age, gender, level of education and smoking, mortality was significantly higher in subjects with diabetic retinopathy, non-glaucomatous optic nerve damage and nuclear cataract. Other major ophthalmic parameters and disorders such as hyperopia, myopia, high myopia, pterygium, age-related macular degeneration, retinal vein occlusion, glaucoma and cortical or nuclear cataract were not significantly associated with mortality in the multivariate analysis.