In the eye of the ophthalmologist: the corneal microbiome in microbial keratitis.

PURPOSE: To describe the bacterial findings by a targeted sequencing approach from corneal samples of patients with microbial keratitis and factors influencing culture outcome of indirectly inoculated corneal specimen. METHODS: Prospective inclusion of patients fulfilling predefined criteria of microbial keratitis. Samples from the corneal lesion were collected and dispensed in liquid transport medium, from which both culture and targeted amplification and sequencing of the V3-V4 region of the 16S rRNA gene were carried out. Additional standard corneal culture from the corneal lesions was also performed. Factors influencing culture outcome of indirectly inoculated corneal samples were identified by a multivariate regression model incorporating quantitative data from sequencing. RESULTS: Among the 94 included patients with microbial keratitis, contact lens wear (n = 69; 73%) was the most common risk factor. Contact lens wearers displayed significant differences in the bacterial community composition of the corneal lesion compared to no lens wearers, with higher abundance of Staphylococcus spp., Corynebacterium spp., and Stenotrophomonas maltophilia. Targeted sequencing detected a potential corneal pathogen in the highest proportional abundance among 9 of the 24 (38%) culture-negative patients with microbial keratitis. Age, bacterial density in the sample, and prior antibiotic treatment significantly influenced culture outcome of indirectly inoculated corneal samples. CONCLUSION: Targeted sequencing may provide insights on pathogens in both culture negative episodes of microbial keratitis and among subgroups of patients with microbial keratitis as well as factors influencing culture outcome of indirectly inoculated corneal samples.

Clinical and genomic features of Corynebacterium macginleyi-associated infectious keratitis.

Infectious keratitis is a potentially sight threatening ophthalmological emergency. Contact lens wear is a common risk factor. Diagnostic advances such as MALDI-TOF MS provides new insights into the spectrum of corneal pathogens and on microbes previously considered as commensals. Corynebacterium macginleyi was described in 1995, and in 2018, the genomic features of three isolates were reported after whole-genome sequencing. Here we describe the clinical characteristics of patients with infectious keratitis (n = 29) presumably caused by Corynebacterium macginleyi, and analyze the genomic features of C. macginleyi (n = 22) isolated from the corneal ulcers of these patients. The disease course was uneventful apart from minor interventions such as corneal cross-linking and amniotic membrane transplant. Genome sequencing and comparison revealed a highly conserved core genome of C. macginleyi. Based on the analyses of single nucleotide polymorphisms, the population could be divided into two main clades that also differed in a few clade-specific genomic islands. Patients infected with an isolate belonging to the minor clade (n = 7) presented a more severe disease. Comparisons with other corynebacterial species clearly separated C. macginleyi. C. macginleyi may be considered a corneal pathogen; genomic analysis provided insights into its population structure and disease-causing potential.

Metabolic syndrome and some of its components in relation to risk of cataract extraction. A prospective cohort study of men.

PURPOSE: To evaluate the relationship between metabolic syndrome and some of its components with the incidence of cataract extraction. METHODS: A population-based prospective cohort with a total of 45 049 men, aged 45-79 years, from the Cohort of Swedish Men completed in 1997 a self-administered questionnaire concerning anthropometric measurements and lifestyle factors. The men were followed from 1 January 1998 through 31 December 2012, and the cohort was matched with registers of cataract extraction. The main outcome measure was incident cases of age-related cataract extraction. RESULTS: Over the 15-years of follow-up, 7573 incident cases of cataract extraction were identified. After controlling for potential confounders, the association between single components of metabolic syndrome, abdominal adiposity, diabetes and hypertension and risk of cataract extraction was rate ratio (RR): 1.04; 95% confidence interval (CI): 0.99-1.10, RR: 1.77; 95% CI: 1.64-1.92 and RR: 1.06; 95% CI 1.00-1.13, respectively. The risk of cataract extraction increased with increasing numbers of metabolic syndrome components (p < 0.0001). Men aged 65 years or younger at baseline with all three components of the metabolic syndrome had a relative risk of 2.43 (95% CI: 1.95-3.01) for cataract extraction. CONCLUSION: In this cohort of middle-aged and elderly men, metabolic syndrome with the combination of abdominal adiposity, diabetes and hypertension was associated with an increased risk for cataract extraction, especially among men aged 65 years or younger. These findings put emphasis on the importance of weight control and healthy lifestyle behaviours in order to prevent cataract.

Are increased levels of systemic oxidative stress and inflammation associated with age-related cataract?

Oxidative stress and inflammation may be involved in the etiology of age-related cataract. This study is the first to investigate the association between urinary levels of 8-iso-prostaglandin F2α (PGF2α; as a biomarker for systemic oxidative stress in vivo) and 15-keto-dihydro-PGF2α (as a biomarker for systemic inflammation in vivo) and risk of age-related cataract. We observed in a nested case-control study, including 258 women with incident cataract diagnosis and/or cataract extraction and 258 women without cataract, matched on age and date of urine sample collection that, women with higher levels of urinary 8-iso-PGF2α as compared with lower levels had an increased risk of age-related cataract. There was no difference in 15-keto-dihydro-PGF2α levels between cases and controls. Our observations lead to the hypothesis that higher systemic oxidative stress increases the risk of developing age-related cataract.

Smoking cessation and the risk of cataract: a prospective cohort study of cataract extraction among men.

IMPORTANCE: Smoking is a risk factor for cataract development, but the effect of smoking cessation on the risk of cataract is uncertain. OBJECTIVE: To examine the association between smoking cessation and the risk of cataract extraction. DESIGN, SETTING, AND PARTICIPANTS: A total of 44,371 men, participating in the Cohort of Swedish Men, aged 45 to 79 years, who in 1997 completed a self-administered questionnaire on smoking habits and lifestyle factors. The men were followed up from January 1, 1998, through December 31, 2009. The cohort was matched with the Swedish National Day-Surgery Register and local registers of cataract extraction in the study area. MAIN OUTCOMES AND MEASURES: Incident cases of age-related cataract extraction. RESULTS: During 12 years of follow-up, we identified 5713 incident cases of age-related cataract extraction. Smoking intensity and cumulative dose of smoking were associated with an increased risk of cataract extraction (P for trend <.001). Current smokers of more than 15 cigarettes per day had a 42% increased risk of cataract extraction (rate ratio, 1.42; 95% CI, 1.28-1.58) compared with never smokers after adjustment for age and other potential risk factors. Smoking cessation significantly decreased the risk for cataract extraction with time (P for trend <.001). After more than 20 years since stopping smoking, men with a mean smoking intensity of more than 15 cigarettes per day had a 21% increased risk of cataract extraction (rate ratio, 1.21; 95% CI, 1.06-1.39) compared with never smokers. Among men who smoked 15 cigarettes or less per day, the effect of smoking cessation was observed earlier, but more than 2 decades after smoking cessation, the risk of cataract extraction did not decrease to the level of never smokers (rate ratio, 1.13; 95% CI, 1.04-1.24). CONCLUSIONS AND RELEVANCE: Smoking cessation seems to decrease the risk of cataract extraction with time, although the risk persists for decades. The higher the intensity of smoking, the longer it takes for the increased risk to decline. These findings emphasize the importance of early smoking cessation and preferably the avoidance of smoking.

Total antioxidant capacity of the diet and risk of age-related cataract: a population-based prospective cohort of women.

IMPORTANCE: To our knowledge, no previous epidemiologic study has investigated the association between all antioxidants in the diet and age-related cataract. The total antioxidant capacity (TAC) concept aims to measure the capacity from all antioxidants in the diet by also taking synergistic effects into account. OBJECTIVE: To investigate the association between the TAC of the diet and the incidence of age-related cataract in a population-based prospective cohort of middle-aged and elderly women. DESIGN, SETTING, AND PARTICIPANTS: Questionnaire-based nutrition survey within the prospective Swedish Mammography Cohort study, which included 30,607 women (aged 49-83 years) who were observed for age-related cataract incidence for a mean of 7.7 years. EXPOSURE: The TAC of the diet was estimated using a database of foods analyzed with the oxygen radical absorbance capacity assay. MAIN OUTCOMES AND MEASURES: Information on incident age-related cataract diagnosis and extraction was collected through linkage to registers in the study area. RESULTS: There were 4309 incident cases of age-related cataracts during the mean 7.7 years of follow-up (234,371 person-years). The multivariable rate ratio in the highest quintile of the TAC of the diet compared with the lowest was 0.87 (95% CI, 0.79-0.96; P for trend = .03). The main contributors to dietary TAC in the study population were fruit and vegetables (44.3%), whole grains (17.0%), and coffee (15.1%). CONCLUSIONS AND RELEVANCE: Dietary TAC was inversely associated with the risk of age-related cataract. Future studies examining all antioxidants in the diet in relation to age-related cataract are needed to confirm or refute our findings.

High-dose supplements of vitamins C and E, low-dose multivitamins, and the risk of age-related cataract: a population-based prospective cohort study of men.

We examined the associations of high-dose supplements of vitamins C and E and low-dose multivitamins with the risk of age-related cataract among 31,120 Swedish men, aged 45-79 years, in a population-based prospective cohort. Dietary supplement use was assessed from a questionnaire at baseline in 1998. During follow-up (January 1998-December 2006), 2,963 incident age-related cataract cases were identified. The multivariable-adjusted hazard ratio for men using vitamin C supplements only was 1.21 (95% confidence interval (CI): 1.04, 1.41) in a comparison with that of non-supplement users. The hazard ratio for long-term vitamin C users (≥10 years before baseline) was 1.36 (95% CI: 1.02, 1.81). The risk of cataract with vitamin C use was stronger among older men (>65 years) (hazard ratio = 1.92, 95% CI: 1.41, 2.60) and corticosteroid users (hazard ratio = 2.11, 95% CI: 1.48, 3.02). The hazard ratio for vitamin E use only was 1.59 (95% CI: 1.12, 2.26). Use of multivitamins only or multiple supplements in addition to vitamin C or E was not associated with cataract risk. These results suggest that the use of high-dose (but not low-dose) single vitamin C or E supplements may increase the risk of age-related cataract. The risk may be even higher among older men, corticosteroid users, and long-term users.

Increased risk of cataract among 28,000 patients with celiac disease.

Vitamin deficiencies are prevalent in celiac disease (CD) and are associated with cataract formation, but it is unknown whether persons with CD are at increased risk of cataract. The authors' objective in this population-based cohort study was to determine the risk of cataract among persons with biopsy-verified CD. Data on CD were collected from reports on small intestinal biopsies performed between July 1969 and February 2008 in the 28 regional pathology departments in Sweden. The authors identified 28,756 persons with CD (villous atrophy, Marsh pathology stage 3). For each person with CD, Statistics Sweden selected up to 5 controls matched for age and sex from the Total Population Register. Data on cataract were obtained from the Swedish National Hospital Discharge Register and the National Day-Surgery Register. Cox regression analysis was used to estimate the risk of cataract. During a median follow-up period of 9 years, the authors identified 1,159 cataracts among persons with CD (909 were expected) (hazard ratio = 1.28, 95% confidence interval: 1.19, 1.36). The absolute risk of cataract was 397/100,000 person-years in CD, with an excess risk of 86/100,000 person-years. In conclusion, this study found an increased risk of developing cataract in patients with CD.

Hormone replacement therapy in relation to risk of cataract extraction: a prospective study of women.

OBJECTIVE: To investigate the association between hormone replacement therapy (HRT) and the incidence of cataract extraction among postmenopausal women. DESIGN: Population-based, prospective cohort study. PARTICIPANTS: A total of 30 861 postmenopausal women participating in the Swedish Mammography Cohort, age 49 to 83 years, who completed a self-administered questionnaire in 1997 about hormone status, HRT, and lifestyle factors. METHODS: The women were followed from September 1997 through October 2005. The cohort was matched with registers of cataract extraction in the study area. MAIN OUTCOME MEASURES: Incident operative extraction of age-related cataract. RESULTS: We identified 4324 incident cases of cataract extractions during 98 months of follow-up. In multivariate adjusted analysis, ever use of HRT was associated with a 14% increased risk of cataract extraction (rate ratio [RR], 1.14; 95% confidence interval [CI], 1.07-1.21) compared with those who never used HRT. Current use of HRT was associated with an 18% increased risk of cataract extraction (RR, 1.18; 95% CI, 1.10-1.26). A significant linear trend was observed where increasing duration of HRT usage resulted in an increased risk of cataract extraction (P for trend = 0.006). Multivariate RR for current HRT usage for >10 years was 1.20 (95% CI, 1.06-1.36; P for trend = 0.001). Among women drinking on average >1 drink of alcohol per day, current HRT users had a 42% increased risk (RR, 1.42; 95% CI, 1.11-1.80) for cataract extraction, compared with women who neither used HRT nor alcohol. The risk of cataract extraction among current users of HRT was similar among current smokers and those who never smoked. CONCLUSIONS: Our prospective, population-based study indicates that postmenopausal women using HRT for a long period of time may be at an increased risk for cataract extraction, especially those drinking >1 alcoholic drink daily.

Vitamin C supplements and the risk of age-related cataract: a population-based prospective cohort study in women.

BACKGROUND: Experimental animal studies have shown adverse effects of high-dose vitamin C supplements on age-related cataract. OBJECTIVE: We examined whether vitamin C supplements (approximately 1000 mg) and multivitamins containing vitamin C (approximately 60 mg) are associated with the incidence of age-related cataract extraction in a population-based, prospective cohort of women. DESIGN: Our study included 24,593 women aged 49-83 y from the Swedish Mammography Cohort (follow-up from September 1997 to October 2005). We collected information on dietary supplement use and lifestyle factors with the use of a self-administrated questionnaire. Cataract extraction cases were identified by linkage to the cataract extraction registers in the geographical study area. RESULTS: During the 8.2 y of follow-up (184,698 person-years), we identified 2497 cataract extraction cases. The multivariable hazard ratio (HR) for vitamin C supplement users compared with that for nonusers was 1.25 (95% CI: 1.05, 1.50). The HR for the duration of >10 y of use before baseline was 1.46 (95% CI: 0.93, 2.31). The HR for the use of multivitamins containing vitamin C was 1.09 (95% CI: 0.94, 1.25). Among women aged > or = 65 y, vitamin C supplement use increased the risk of cataract by 38% (95% CI: 12%, 69%). Vitamin C use among hormone replacement therapy users compared with that among nonusers of supplements or of hormone replacement therapy was associated with a 56% increased risk of cataract (95% CI: 20%, 102%). Vitamin C use among corticosteroid users compared with that among nonusers of supplements and corticosteroids was associated with an HR of 1.97 (95% CI: 1.35, 2.88). CONCLUSION: Our results indicate that the use of vitamin C supplements may be associated with higher risk of age-related cataract among women.

Metabolic syndrome components in relation to risk of cataract extraction: a prospective cohort study of women.

OBJECTIVE: To investigate the association between metabolic syndrome and some of its components with the incidence of cataract extraction. DESIGN: Population-based prospective cohort study. PARTICIPANTS: A total of 35,369 women, participating in the Swedish Mammography Cohort, aged 49 to 83 years, who completed a self-administered questionnaire about anthropometric measurements and lifestyle factors in 1997. METHODS: The women were followed from September of 1997 to October of 2005. The cohort was matched with registers of cataract extraction in the study area. MAIN OUTCOME MEASURES: Incident surgical extraction of age-related cataract. RESULTS: We identified 4508 incident cases of cataract extractions during 98 months of follow-up. In multivariate analysis, women with a waist circumference >or=80 cm had an 8% increased risk of cataract extraction (rate ratio [RR], 1.08; 95% confidence interval [CI], 0.99-1.17). Women with diabetes had a 43% increased risk of cataract extraction (RR, 1.43; 95% CI, 1.10-1.86), and hypertension was associated with a 12% increased risk (RR, 1.12; 95% CI, 0.99-1.26). Women with all 3 components of the metabolic syndrome (waist >or=80 cm, diabetes, and hypertension) had a 68% increased risk of cataract extraction (RR, 1.68; 95% CI, 1.40-2.02) compared with women without any of these components. Among women aged less than 65 years at baseline with all 3 components of metabolic syndrome, the risk of cataract extraction was approximately 3-fold more (RR, 2.80; CI, 1.94-4.03). CONCLUSIONS: Metabolic syndrome and its components, abdominal adiposity, diabetes, and hypertension, seem to be associated with an increased risk for cataract extraction, especially among women aged less than 65 years.

Alcohol consumption and risk of cataract extraction: a prospective cohort study of women.

PURPOSE: To investigate the association between alcohol consumption and the risk of cataract extraction. DESIGN: Population-based prospective cohort study. PARTICIPANTS: A total of 34,713 women participating in the Swedish Mammography Cohort, age 49 to 83 years, completed in 1997 a self-administered questionnaire about alcohol, smoking, and other lifestyle factors. METHODS: The women were followed from September 1997 through September 2004. The cohort was matched with registers of cataract extraction from the study area. MAIN OUTCOME MEASURES: Incident surgical extraction of age-related cataract. RESULTS: During 84 months of follow-up, we found 3587 incident cases of age-related cataract extraction. Compared with never drinkers, the relative risk of cataract extraction among current drinkers was 1.11 (95% confidence interval [CI] 1.02-1.21) after adjustment for age and other potential risk factors. In multivariate analysis, an increment of 13 g alcohol intake per day (corresponding to 1 drink = 330 ml of beer, 150 ml of wine, or 45 ml of liquor) was associated with a 7% increased risk of cataract extraction (relative risk, 1.07; 95% CI 1.02-1.12). Mean age at cataract extraction among nonsmoking women who used alcohol was 75 years, compared with 77.6 years among never drinkers. CONCLUSIONS: These prospective data suggest that daily use of >/=1 alcoholic drinks was associated with a modest increase of risk for cataract extraction. The risk increased with increasing alcohol consumption.

Intensity of smoking and smoking cessation in relation to risk of cataract extraction: a prospective study of women.

The authors investigated the association of smoking and smoking cessation with the incidence of cataract extraction in a population-based prospective cohort study. A total of 34,595 women aged 49-83 years in the Swedish Mammography Cohort were followed from September 1997 through June 2002. Information on smoking, diet, and other lifestyle factors was collected through a self-administered questionnaire. A total of 2,128 cases of age-related cataract extraction were identified. Relative risks were estimated as rate ratios using Cox proportional hazards models. The authors observed a significant dose-response association between intensity of smoking and risk of cataract extraction (among current smokers, p for trend = 0.02; among past smokers, p for trend = 0.0002). After cessation of smoking, the risk decreased with time. Among women with a moderate lifetime smoking intensity (6-10 cigarettes/day), the relative risk was not significantly different from the risk among never smokers 10 years after smoking cessation. Among women who had smoked more intensively (>10 cigarettes/day), after 20 years of nonsmoking the increased risk became small and no longer statistically significant in comparison with never smokers (for trend over time, p < 0.0001). This prospective study confirmed smoking as a risk factor for cataract, with a dose response for smoking intensity. Smoking cessation predicts reduced risk over time, but a longer period of time is needed with a higher smoking intensity.