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.

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.

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.

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.

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.

Cataract, visual impairment and long-term mortality in a rural cohort in India: the Andhra Pradesh Eye Disease Study.

BACKGROUND: A large-scale prevalence survey of blindness and visual impairment (The Andhra Pradesh Eye Diseases Study [APEDS1]) was conducted between 1996-2000 on 10,293 individuals of all ages in three rural and one urban clusters in Andhra Pradesh, Southern India. More than a decade later (June 2009-March 2010), APEDS1 participants in rural clusters were traced (termed APEDS2) to determine ocular risk factors for mortality in this longitudinal cohort. METHODS AND FINDINGS: Mortality hazard ratio (HR) analysis was performed for those aged >30 years at APEDS1, using Cox proportional hazard regression models to identify associations between ocular exposures and risk of mortality. Blindness and visual impairment (VI) were defined using Indian definitions. 799/4,188 (19.1%) participants had died and 308 (7.3%) had migrated. Mortality was higher in males than females (p<0.001). In multivariable analysis, after adjusting for age, gender, diabetes, hypertension, body mass index, smoking and education status the mortality HR was 1.9 (95% CI: 1.5-2.5) for blindness; 1.4 (95% CI: 1.2-1.7) for VI; 1.8 (95% CI: 1.4-2.3) for pure nuclear cataract, 1.5 (95% CI: 1.1-2.1) for pure cortical cataract; 1.96 (95% CI: 1.6-2.4) for mixed cataract, 2.0 (95% CI: 1.4-2.9) for history of cataract surgery, and 1.58 (95% CI: 1.3-1.9) for any cataract. When all these factors were included in the model, the HRs were attenuated, being 1.5 (95% CI: 1.1-2.0) for blindness and 1.2 (95% CI: 0.9-1.5) for VI. For lens type, the HRs were as follows: pure nuclear cataract, 1.6 (95% CI: 1.3-2.1); pure cortical cataract, 1.5 (95% CI: 1.1-2.1); mixed cataract, 1.8 (95% CI: 1.4-2.2), and history of previous cataract surgery, 1.8 (95% CI: 1.3-2.6). CONCLUSIONS: All types of cataract, history of cataract surgery and VI had an increased risk of mortality that further suggests that these could be potential markers of ageing.

Cataract and mortality. The Beijing eye study.

BACKGROUND: To assess an association between cataract and mortality in a population-based setting. METHODS: At baseline in 2001, the Beijing Eye Study examined 4255 subjects for cataract using standardized lens photographs which were examined according to the Age-Related Eye Disease Study scheme. In 2006, all study participants were re-invited for a follow-up examination. RESULTS: Out of the 4255 subjects, 3142 subjects (73.8%) returned for follow-up examination, while 135 subjects (3.2%) were dead and 978 subjects (23.0%) did not agree to be re-examined or had moved away. In multivariate analysis, the amount subcapsular cataract was significantly associated with increased mortality (P = 0.029; OR: 2.14; 95%CI: 1.08, 4.25), particularly for the subjects with an age of 65+ years and 70+ years (P = 0.016 and P = 0.003 respectively). Correspondingly, product of age times amount of subcapsular cataract was significantly associated with mortality (P = 0.001). Degree of nuclear cataract and amount of cortical cataract were not associated with mortality in multivariate analysis (P = 0.910 and P = 0.938 respectively). CONCLUSIONS: As also found in previous epidemiological studies on Western populations, cataract, namely subcapsular cataract in elderly subjects, is associated with an increased mortality risk.

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.

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.

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.

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.

Orbital irradiation for Graves' ophthalmopathy: Is it safe? A long-term follow-up study.

PURPOSE: We evaluated the frequency of long-term complications of orbital irradiation (radiation-induced tumors, cataract, and retinopathy) in comparison with glucocorticoids. DESIGN: We conducted a follow-up study in a cohort of 245 Graves' ophthalmopathy patients who had been treated with retrobulbar irradiation (20 Gy in 2 weeks) and/or oral glucocorticoids between 1982 and 1993 in our institution. Irradiated patients were compared with nonirradiated patients. METHODS: Data on mortality and cause of death were obtained. Living patients were invited to participate in a follow-up study. Possible retinopathy was assessed in a masked fashion and defined as the presence of > or =1 hemorrhages and/or microaneurysms on red-free retina photographs. If >5 lesions were present, patients were categorized as suffering from definite retinopathy. Cataract was assessed using the Lens Opacity Classification System II score. MAIN OUTCOME MEASURES: Mortality, prevalence of retinopathy, prevalence of cataract, and type of cataract. RESULTS: Thirty-seven of the 245 patients had died, none of them from an intracranial tumor. Mortality was similar in the irradiated (27/159 [17%]) and nonirradiated patients (10/86 [12%]; P = 0.264). One hundred fifty-seven of the 208 living patients (75%) consented to participate in a follow-up ophthalmologic investigation; the mean follow-up time (+/- standard deviation) was 11+/-3 years. Possible retinopathy was present in 15% of patients, 22 of the irradiated and 1 of the nonirradiated patients (P = 0.002). In 5 patients (all had been irradiated), definite retinopathy (i.e., >5 retinal lesions) was present. Of these, 3 had diabetes mellitus, and 1 had hypertension. Diabetes was associated with both possible (P = 0.029) and definite (P = 0.005) retinopathy, with a relative risk of 21 (95% confidence interval, 3-179). The prevalence and severity of cataract were similar in the radiotherapy group (29%) and the glucocorticoid group (34%); it should be noted that 88 of 104 of the irradiated patients were also treated with oral glucocorticoids. CONCLUSION: The data suggest that orbital irradiation for Graves' ophthalmopathy is a safe treatment modality, except possibly for diabetic patients.

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.

Association between lens opacities and mortality in the Priverno Eye Study.

BACKGROUND: Lens opacities are associated with a higher risk of death, although there are some discrepancies regarding the specific types of cataract representing risk. The purpose of the present study was to further investigate the relationships between different types of lens opacity and patient survival. METHODS: In 1987, 860 residents of Priverno, Italy, aged 45-69 years underwent an ophthalmologic examination. Based on patient histories and the findings of the slit-lamp examination, each of the 860 patients was classified according to the type of opacity (pure cortical, pure nuclear, pure posterior subcapsular, mixed, and surgical aphakia). The survivors of the original cohort were re-examined in 1994. Death and survival rates were computed by the Kaplan-Meier method. Associations between mortality and significant factors were included in a stepwise Cox proportional-hazards regression model. RESULTS: Forty-four members of the original cohort had died during the 7-year follow-up. Age-adjusted survival curves based on Kaplan-Meier estimates showed significantly lower survival in those whose baseline examinations had revealed pure nuclear opacity (log rank test: P=0.020) and aphakia (log rank test: P<0.001). When adjusted for other mortality risk factors (age, sex, diabetes, cardiovascular diseases), the hazard ratio was 4.32 for pure nuclear opacity (95% CI 1.13-16.4) and 18.3 for aphakia (95% CI 3.21-104.0). CONCLUSIONS: The analysis of the Priverno data seems to confirm an association between lower survival and cataracts, particularly those confined to the lens nucleus and those that had already prompted surgery.

Is there a direct association between age-related eye diseases and mortality? The Rotterdam Study.

PURPOSE: To study mortality in subjects with age-related maculopathy (ARM), cataract, or open-angle glaucoma (OAG) in comparison with those without these disorders. DESIGN: Population-based prospective cohort study. PARTICIPANTS: Subjects (n = 6339) aged 55 years and older from the population-based Rotterdam Study for whom complete information on eye disease status was present. MAIN OUTCOME MEASURES: Vital status continuously monitored from 1990 until January 1, 2000. METHODS: The diagnosis of ARM was made according to the International Classification System. Cataract, determined on biomicroscopy, was defined as any sign of nuclear or (sub)cortical cataract, or both, in at least one eye with a visual acuity of 20/40 or less. Aphakia and pseudophakia in at least one eye were classified as operated cataract. Definite OAG was defined as a glaucomatous optic neuropathy combined with a glaucomatous visual field defect. Diagnoses were assessed at baseline. Mortality hazard ratios were computed using Cox proportional hazard regression analysis, adjusted for appropriate confounders (age, gender, smoking status, body mass index, cholesterol level, atherosclerosis, hypertension, history of cardiovascular disease, and diabetes mellitus). RESULTS: The adjusted mortality hazard ratio for subjects with AMD (n = 104) was 0.94 (95% confidence interval [CI], 0.52-1.68), with biomicroscopic cataract (n = 951) was 0.94 (95% CI, 0.74-1.21), with surgical cataract (n = 298) was 1.20 (95% CI, 0.86-1.68), and with definite OAG (n = 44) was 0.39 (95% CI, 0.10-1.55). CONCLUSIONS: Both ARM and cataract are predictors of shorter survival because they have risk factors that also affect mortality. When adjusted for these factors, ARM, cataract, and OAG were themselves not significantly associated with mortality.

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.